PNEUMOVAX 23

אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ(

05.2013

__ ךיראת

.

10.1310

___________

םושירה רפסמו תילגנאב רישכת םש

Pneumovax 23 )136.52.23874.00(

םושירה לעב םש

Merck, Sharp & Dohme (Israel-1996) Ltd

.

__________

! דבלב תורמחהה טורפל דעוימ הז ספוט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט

Adverse events

:תואבה יאוולה תועפות ופסונ

Tenderness, Ecchymosis, Pruritus, Diarrhea,

Dyspepsia, Back Pain, Neck Pain, Upper

respiratory infection, Pharyngitis, Erythema

multiforme

Concomitant

Administration

with Other

Vaccines

In a double-blind, controlled clinical trial, 473

adults, 60 years of age or older, were randomized

receive

ZOSTAVAX

PNEUMOVAX

concomitantly (N=237), or PNEUMOVAX

23 alone

followed 4 weeks later by ZOSTAVAX alone

(N=236).

four

weeks

postvaccination,

varicella-zoster

virus

(VZV)

antibody

levels

following concomitant use were significantly lower

than

antibody

levels

following

nonconcomitant administration (GMTs of 338 vs.

484 gp ELISA units/mL, respectively; GMT ratio =

0.70 (95% CI: [0.61, 0.80]).

Limited safety and immunogenicity data from

clinical trials are available on the concurrent

administration

PNEUMOVAX

vaccines other than ZOSTAVAX

PNEUMOVAX

®

23

Pneumococcal Vaccine Polyvalent

Solution for S.C or I.M Injection

1

INDICATIONS AND USAGE

PNEUMOVAX 23 is indicated for vaccination against pneumococcal disease caused by those pneumococcal

types included in the vaccine.

Effectiveness of the vaccine in the prevention of pneumococcal pneumonia and pneumococcal bacteremia

has been demonstrated in controlled trials in South Africa, France and in case-control studies.

PNEUMOVAX 23 will not prevent disease caused by capsular types of pneumococcus other than those

contained in the vaccine.

Vaccination with PNEUMOVAX 23 is recommended for selected individuals as follows:

− routine vaccination for persons 50 years of age or older

− persons aged ≥ 2 years with certain chronic conditions or in special environments or social settings.

Specific recommendations for the prevention of pneumococcal disease can be found at the following

address: http://www.health.gov.il/PublicationsFiles/tadrich_Chisunim.pdf

2

DOSAGE AND ADMINISTRATION

For intramuscular or subcutaneous injection only.

2.1

Preparation

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to

administration. If either of these two conditions exists, the vaccine should not be administered.

Do not mix PNEUMOVAX 23 with other vaccines in the same syringe or vial.

Use a separate sterile syringe and needle for each individual patient to prevent transmission of

infectious agents from one person to another.

Single-Dose Vial

Withdraw 0.5 mL from the vial using a sterile needle and syringe free of preservatives, antiseptics, and

detergents.

Single-Dose, Prefilled Syringe

The package contains 2 needles. Attach the sterile needle to the prefilled syringe by twisting in a clockwise

direction until the needle fits securely on the syringe.

2.2

Administration

Administer PNEUMOVAX 23 intramuscularly or subcutaneously into the deltoid muscle or lateral mid-thigh.

Do not inject intravascularly or intradermally.

Single-Dose Vial

Administer a single 0.5-mL dose of PNEUMOVAX 23 using a sterile needle and syringe.

Single-Dose, Prefilled Syringe

Administer the entire contents of the single-dose, prefilled syringe per standard protocol using a sterile

needle.

2.3 Revaccination

The Advisory Committee on Immunization Practices (ACIP) has recommendations for revaccination against

pneumococcal disease for persons at high risk who were previously vaccinated with PNEUMOVAX 23.

Routine revaccination of immunocompetent persons previously vaccinated with a 23-valent vaccine, is not

recommended.

3

DOSAGE FORMS AND STRENGTHS

PNEUMOVAX 23 is a clear, sterile solution supplied in a (0.5-mL dose) single-dose vial and a single-dose

prefilled syringe [See Description (11) and How Supplied/Storage and Handling (16).]

4

CONTRAINDICATIONS

4.1

Hypersensitivity

Do not administer PNEUMOVAX 23 to individuals with a history of anaphylactic/anaphylactoid or severe

allergic reaction to any component of the vaccine [See Description (11)].

5

WARNINGS AND PRECAUTIONS

5.1

Persons with Moderate or Severe Acute Illness

Defer vaccination with PNEUMOVAX 23 in persons with moderate or severe acute illness.

5.2

Persons with Severely Compromised Cardiovascular or Pulmonary Function

Caution and appropriate care should be exercised in administering PNEUMOVAX 23 to individuals with

severely compromised cardiovascular and/or pulmonary function in whom a systemic reaction would pose a

significant risk.

5.3

Use of Antibiotic Prophylaxis

This vaccine does not replace the need for penicillin (or other antibiotic) prophylaxis against pneumococcal

infection. In patients who require penicillin (or other antibiotic) prophylaxis against pneumococcal infection,

such prophylaxis should not be discontinued after vaccination with PNEUMOVAX 23.

5.4

Persons with Altered Immunocompetence

Persons who are immunocompromised, including persons receiving immunosuppressive therapy, may have

a diminished immune response to PNEUMOVAX 23. [See Use in Specific Populations (8.6).]

5.5

Persons with Chronic Cerebrospinal Fluid Leakage

PNEUMOVAX 23 may not be effective in preventing pneumococcal meningitis in patients who have chronic

cerebrospinal

fluid

(CSF)

leakage

resulting

from

congenital

lesions,

skull

fractures,

neurosurgical

procedures.

6

ADVERSE REACTIONS

The most common adverse reactions, reported in >10% of subjects vaccinated with PNEUMOVAX 23 in

clinical

trials

were:

injection-site

pain/soreness/tenderness

(60.0%),

injection-site

swelling/induration

(20.3%), headache (17.6%), injection-site erythema (16.4%), asthenia/fatigue (13.2%), and myalgia (11.9%).

[See Adverse Reactions (6.1).]

6.1

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the

clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and

may not reflect the rates observed in practice.

In a randomized, double-blind, placebo-controlled crossover clinical trial, subjects were enrolled in four

different cohorts defined by age (50-64 years of age and ≥65 years of age) and vaccination status (no

pneumococcal vaccination or receipt of a pneumococcal polysaccharide vaccine 3-5 years prior to the

study). Subjects in each cohort were randomized to receive intramuscular injections of PNEUMOVAX 23

followed by placebo (saline containing 0.25% phenol), or placebo followed by PNEUMOVAX 23, at 30-day

(±7 days) intervals. The safety of an initial vaccination (first dose) was compared to revaccination (second

dose) with PNEUMOVAX 23 for 14 days following each vaccination.

All 1008 subjects (average age, 67 years; 49% male and 51% female; 91% Caucasian, 4.7% African-

American, 3.5% Hispanic, and 0.8% Other) received placebo injections.

Initial vaccination was evaluated in a total of 444 subjects (average age 65 years; 32% male and 68%

female; 93% Caucasian, 3.2% African-American, 3.4% Hispanic, and 1.1% Other).

Revaccination was evaluated in 564 subjects (average age 69 years; 53% male and 47% female; 90%

Caucasian, 3.5% Hispanic, 6.0% African-American, and 0.5% Other).

Serious Adverse Experiences

In this study, 10 subjects had serious adverse experiences within 14 days of vaccination: 6 who received

PNEUMOVAX

received

placebo.

Serious

adverse

experiences

within

days

after

PNEUMOVAX 23 included angina pectoris, heart failure, chest pain, ulcerative colitis, depression, and

headache/tremor/stiffness/sweating. Serious adverse experiences within 14 days after placebo included

myocardial infarction complicated with heart failure, alcohol intoxication, angina pectoris, and edema/urinary

retention/heart failure/diabetes.

Five subjects reported serious adverse experiences that occurred outside the 14-day follow-up window: 3

received

PNEUMOVAX

received

placebo.

Serious

adverse

experiences

after

PNEUMOVAX 23 included cerebrovascular accident, lumbar radiculopathy, and pancreatitis/myocardial

infarction resulting in death. Serious adverse experiences after placebo included heart failure and motor

vehicle accident resulting in death.

Solicited and Unsolicited Reactions

Table 1 presents the adverse event rates for all solicited and unsolicited reactions reported in ≥1% in any

group in this study, without regard to causality.

The most common local adverse reactions reported at the injection site after initial vaccination with

PNEUMOVAX

were

pain/tenderness/soreness

(60.0%),

swelling/induration

(20.3%),

erythema

(16.4%). The most common systemic adverse experiences

were headache (17.6%), asthenia/fatigue

(13.2%), and myalgia (11.9%).

most

common

local

adverse

reactions

reported

injection

site

after

revaccination

with

PNEUMOVAX 23 were pain/soreness/tenderness (77.2%), swelling (39.8%), and erythema (34.5%). The

most common systemic adverse reactions with revaccination were headache (18.1%), asthenia/fatigue

(17.9%), and myalgia (17.3%). All of these adverse reactions were reported at a rate lower than 10% after

receiving a placebo injection.

Table 1: Incidence of Injection-Site and Systemic Complaints in Adults ≥50 Years of Age Receiving Their First (Initial)

or Second (Revaccination) Dose of PNEUMOVAX 23 (Pneumococcal Polysaccharide Vaccine, 23 Valent) or Placebo

Occurring at ≥1% in Any Group

PNEUMOVAX 23

Initial Vaccination

N=444

PNEUMOVAX 23

Revaccination*

N=564

Placebo Injection

†

N=1008

Number Followed for Safety

AE Rate

AE Rate

AE Rate

Injection-Site Complaints

Solicited Events

Pain/Soreness/Tenderness

60.0%

77.2%

7.7%

Swelling/Induration

20.3%

39.8%

2.8%

Erythema

16.4%

34.5%

3.3%

Unsolicited Events

Ecchymosis

1.1%

0.3%

Pruritus

0.2%

1.6%

0.0%

Systemic Complaints

Solicited Events

Asthenia/Fatigue

13.2%

17.9%

6.7%

Chills

2.7%

7.8%

1.8%

Myalgia

11.9%

17.3%

3.3%

Headache

17.6%

18.1%

8.9%

Unsolicited Events

Fever

1.4%

2.0%

0.7%

Diarrhea

1.1%

0.7%

0.5%

Dyspepsia

1.1%

1.1%

0.9%

Nausea

1.8%

1.8%

0.9%

Back Pain

0.9%

0.9%

1.0%

Neck Pain

0.7%

1.5%

0.2%

Upper Respiratory

Infection

1.8%

2.6%

1.8%

Pharyngitis

1.1%

0.4%

1.3%

*Subjects receiving their second dose of pneumococcal polysaccharide vaccine as PNEUMOVAX 23 approximately 3-5 years

after their first dose.

Subjects receiving placebo injection from this study combined over periods.

The number of subjects receiving placebo followed for injection-site complaints. The corresponding number of subjects

followed for systemic complaints was 981.

Fever events include subjects who felt feverish in addition to subjects with elevated temperature.

In this clinical study an increased rate of local reactions was observed with revaccination at 3-5 years

following initial vaccination.

For subjects aged 65 years or older, injection-site adverse reaction rate was higher following revaccination

(79.3%)

than

following

initial

vaccination

(52.9%).

proportion

subjects

reporting

injection

site

discomfort that interfered with or prevented usual activity or injection site induration ≥4 inches was higher

following revaccination (30.6%) than following initial vaccination (10.4%). Injection site reactions typically

resolved by 5 days following vaccination.

For subjects aged 50-64 years, the injection-site adverse reaction rate for revaccinees and initial vaccinees

was similar (79.6% and 72.8% respectively).

The rate of systemic adverse reactions was similar among both initial vaccinees and revaccinees within each

age group. The rate of vaccine-related systemic adverse reactions was higher following revaccination

(33.1%) than following initial vaccination (21.7%) in subjects 65 years of age or older, and was similar

following revaccination (37.5%) and initial vaccination (35.5%) in subjects 50-64 years of age. The most

common systemic adverse reactions reported after PNEUMOVAX 23 were as follows: asthenia/fatigue,

myalgia and headache.

Regardless of age, the observed increase in post vaccination use of analgesics (≤13% in the revaccinees

and ≤4% in the initial vaccinees) returned to baseline by day 5.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows

continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the National

Regulation by using an online form:

http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il

6.2

Post-Marketing Experience

following

list

adverse

reactions

includes

those

identified

during

post

approval

PNEUMOVAX 23. Because these reactions are reported voluntarily from a population of uncertain size, it is

not always possible to reliably estimate their frequency or their causal relationship to product exposure.

General disorders and administration site conditions

Cellulitis

Malaise

Fever (>38.9°C)

Warmth at the injection site

Decreased limb mobility

Peripheral edema in the injected extremity

Digestive System

Nausea

Vomiting

Hematologic/ Lymphatic

Lymphadenitis

Lymphadenopathy

Thrombocytopenia in patients with stabilized idiopathic thrombocytopenic purpura

Hemolytic anemia in patients who have had other hematologic disorders

Leukocytosis

Hypersensitivity reactions including

Anaphylactoid reactions

Serum Sickness

Angioneurotic edema

Musculoskeletal System

Arthralgia

Arthritis

Nervous System

Paresthesia

Radiculoneuropathy

Guillain-Barré syndrome

Febrile convulsion

Skin

Rash

Urticaria

Cellulitis-like reactions

Erythema multiforme

Investigations

Increased serum C-reactive protein

7

DRUG INTERACTIONS

7.1

Concomitant Administration with Other Vaccines

In a randomized clinical study, a reduced immune response to ZOSTAVAX® as measured by gpELISA was

observed in individuals who received concurrent administration of PNEUMOVAX 23 and ZOSTAVAX

compared with individuals who received these vaccines 4 weeks apart. Consider administration of the two

vaccines separated by at least 4 weeks. [See Clinical Studies (14.3).]

Limited safety and immunogenicity data from clinical trials are available on the concurrent administration of

PNEUMOVAX 23 and vaccines other than ZOSTAVAX.

8

USE IN SPECIFIC POPULATIONS

8.1

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with PNEUMOVAX 23. It is

also not known whether PNEUMOVAX 23 can cause fetal harm when administered to a pregnant woman or

can affect reproduction capacity. PNEUMOVAX 23 should be given to a pregnant woman only if clearly

needed.

8.3

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human

milk, caution should be exercised when PNEUMOVAX 23 is administered to a nursing woman.

8.4

Pediatric Use

PNEUMOVAX 23 is not approved for use in children less than 2 years of age. Children in this age group do

not develop an effective immune response to the capsular types contained in this polysaccharide vaccine.

The ACIP has recommendations for use of PNEUMOVAX 23 in children 2 years of age or older, who have

previously received pneumococcal vaccines, and who are at increased risk for pneumococcal disease.

8.5

Geriatric Use

In one clinical trial of PNEUMOVAX 23, conducted post-licensure, a total of 629 subjects who were aged ≥65

years and 201 subjects who were aged ≥75 years were enrolled.

In this trial, the safety of PNEUMOVAX 23 in adults 65 years of age and older (N=629) was compared to the

safety of PNEUMOVAX 23 in adults 50 to 64 years of age (N=379). The subjects in this study had underlying

chronic illness but were in stable condition; at least 1 medical condition at enrollment was reported by 86.3%

of subjects who were 50 to 64 years old, and by 96.7% of subjects who were 65 to 91 years old. The rate of

vaccine-related systemic adverse experiences was higher following revaccination (33.1%) than following

primary vaccination (21.7%) in subjects ≥65 years of age, and was similar following revaccination (37.5%)

and primary vaccination (35.5%) in subjects 50 to 64 years of age.

Since 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.

Post-marketing

reports

have

been

received

which

some

elderly

individuals

severe

adverse

experiences and a complicated clinical course following vaccination. Some individuals with underlying

medical conditions of varying severity experienced local reactions and fever associated

with clinical

deterioration requiring hospital care.

8.6

Immunocompromised Individuals

Persons who are immunocompromised, including persons receiving immunosuppressive therapy, may have

a diminished immune response to PNEUMOVAX 23.

11

DESCRIPTION

PNEUMOVAX 23 (Pneumococcal Vaccine Polyvalent) is a sterile, liquid vaccine consisting of a mixture of

purified capsular polysaccharides from Streptococcus pneumoniae types (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V,

10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F).

PNEUMOVAX 23 is a clear, colorless solution. Each 0.5-mL dose of vaccine contains 25 micrograms of

each polysaccharide type. Also contains 0.25% phenol as a preservative, sodium chloride and water for

injections. The vaccine is used directly as supplied. No dilution or reconstitution is necessary.

The vial stoppers, syringe plunger stopper and syringe tip cap are not made with natural rubber latex.

12

CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

PNEUMOVAX 23 induces type-specific antibodies that enhance opsonization, phagocytosis, and killing of

pneumococci by leukocytes and other phagocytic cells. The levels of antibodies that correlate with protection

against pneumococcal disease have not been clearly defined.

14

CLINICAL STUDIES

14.1 Effectiveness

The protective efficacy of pneumococcal vaccines containing six (types 1, 2, 4, 8, 12F, and 25) or twelve

(types 1, 2, 3, 4, 6A, 8, 9N, 12F, 25, 7F, 18C, and 46) capsular polysaccharides was investigated in two

controlled studies in South Africa in male novice gold miners ranging in age from 16 to 58 years, in whom

there was a high attack rate for pneumococcal pneumonia and bacteremia.

4

In both studies, participants in

the control groups received either meningococcal polysaccharide serogroup A vaccine or saline placebo. In

both studies, attack rates for vaccine type pneumococcal pneumonia were observed for the period from 2

weeks through about 1 year after vaccination. Protective efficacy was 76% and 92%, respectively, for the 6-

and 12-valent vaccines, for the capsular types represented.

Three

similar

studies

South

African

young

adult

male

novice

gold

miners

were

carried

Dr. R. Austrian and associates

using similar pneumococcal vaccines prepared for the National Institute of

Allergy and Infectious Diseases, with pneumococcal vaccines containing a 6-valent formulation (types 1, 3,

4, 7, 8, and 12) or a 13-valent formulation (types 1, 2, 3, 4, 6, 7, 8, 9, 12, 14, 18, 19, and 25) capsular

polysaccharides. The reduction in pneumococcal pneumonia caused by the capsular types contained in the

vaccines was 79%. Reduction in type-specific pneumococcal bacteremia was 82%.

A prospective study in France found a pneumococcal vaccine containing fourteen (types 1, 2, 3, 4, 6A, 7F, 8,

9N, 12F, 14, 18C, 19F, 23F, and 25) capsular polysaccharides to be 77% (95%CI: 51% to 89%) effective in

reducing the incidence of pneumonia among male and female nursing home residents with a mean age of

74 (standard deviation of 4 years).

In a study using a pneumococcal vaccine containing eight (types 1, 3, 6, 7, 14, 18, 19, and 23) capsular

polysaccharides, vaccinated children and young adults aged 2 to 25 years who had sickle cell disease,

congenital asplenia, or undergone a splenectomy experienced significantly less bacteremic pneumococcal

disease than patients who were not vaccinated.

In the United States, one post-licensure randomized controlled trial, in the elderly or patients with chronic

medical conditions

who received a 14-valent pneumococcal polysaccharide vaccine (types 1, 2, 3, 4, 6A, 8,

9N, 12F, 14, 19F, 23F, 25, 7F, and 18C), did not support the efficacy of the vaccine for nonbacteremic

pneumonia.

A retrospective cohort analysis study based on the U.S. Centers for Disease Control and Prevention (CDC)

pneumococcal surveillance system, showed 57% (95%CI: 45% to 66%) overall protective effectiveness

against invasive infections caused by serotypes included in PNEUMOVAX 23 in persons

6 years of age, 65

to 84% effectiveness among specific patient groups (e.g., persons with diabetes mellitus, coronary vascular

disease, congestive heart failure, chronic pulmonary disease, and anatomic asplenia) and 75% (95%CI: 57%

to 85%) effectiveness in immunocompetent persons aged

65 years of age. Vaccine effectiveness could not

be confirmed for certain groups of immunocompromised patients.

14.2 Immunogenicity

The levels of antibodies that correlate with protection against pneumococcal disease have not been clearly

defined.

Antibody responses to most pneumococcal capsular types are generally low or inconsistent in children less

than 2 years of age.

14.3 Concomitant Administration with Other Vaccines

In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized to receive

ZOSTAVAX and PNEUMOVAX

23 concomitantly (N=237), or PNEUMOVAX

23 alone followed 4 weeks later

by ZOSTAVAX alone (N=236). At four weeks postvaccination, the varicella-zoster virus (VZV) antibody

levels

following

concomitant

were

significantly

lower

than

antibody

levels

following

nonconcomitant administration (GMTs of 338 vs. 484 gp ELISA units/mL, respectively; GMT ratio = 0.70

(95% CI: [0.61, 0.80]).

Limited safety and immunogenicity data from clinical trials are available on the concurrent administration of

PNEUMOVAX 23 and vaccines other than ZOSTAVAX.

15

REFERENCES

Centers for Disease Control and Prevention. Prevention of Pneumococcal Disease. Recommendations of the Advisory

Committee

Immunization

Practices

(ACIP).

MMWR.

46(No.

RR-8):

1-25,

1997.

Available

from:

http://www.cdc.gov/mmwr/PDF/rr/rr4608.pdf

Centers for Disease Control and Prevention. Prevention of Pneumococcal Disease Among Infants and Children --- Use of 13-

Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine, MMWR 59(RR11): 1-18,

2010. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5911a1.htm?s_cid=rr5911a1_e

Kelton, J.G.: Vaccination-associated relapse of immune thrombocytopenia, JAMA. 245(4): 369-371, 1981.

Smit,

Oberholzer,

Hayden-Smith,

Koornhof,

H.J.;

Hilleman,

M.R.:

Protective

efficacy

pneumococcal

polysaccharide vaccines, JAMA. 238: 2613-2616, 1977.

Austrian, R.; Douglas, R.M.; Schiffman, G.; Coetzee, A.M.; Koornhof, H.J.; Hayden-Smith, S.; Reid, R.D.W.: Prevention of

pneumococcal pneumonia by vaccination, Trans. Assoc. Am. Physicians. 89: 184-194, 1976.

Gaillat, J.; Zmirou, D.; Mallaret, M.R.: Essai clinique du vaccin antipneuomococcique chez des personnes agees vivant en

institution, Rev. Epidemiol. Sante Publique. 33: 437-44, 1985.

Ammann, A.J.; Addiego, J.; Wara, D.W.; Lubin, B.; Smith, W.B.; Mentzer, W.C.: Polyvalent pneumococcal-polysaccharide

immunization of patients with sickle-cell anemia and patients with splenectomy, N. Engl. J. Med. 297: 897-900, 1977.

Simberkoff, M.S.; Cross, A.P.; Al-Ibrahim, M.: Efficacy of pneumococcal vaccine in high risk patients: results of a Veterans

Administration cooperative study, N. Engl. J. Med. 315: 1318-27, 1986.

Butler, J.C.; Breiman, R.F.; Campbell, J.F.; Lipman, H.B.; Broome, C.V.; Facklam, R.R.: Pneumococcal polysaccharide

vaccine efficacy. An evaluation of current recommendations, JAMA. 270: 1826-31, 1993.

Vaccine Adverse Event Reporting System - United States, MMWR. 39(41): 730-33, October 19, 1990.

16

HOW SUPPLIED/STORAGE AND HANDLING

PNEUMOVAX

23 is supplied as follows:

A carton with 1 single-dose vial.

A carton with 1 single-dose, pre-filled Luer-Lok™ syringe with 2 needles.

Storage and Handling

Store at 2-8°C. Do not freeze.

The expiry date of the product is indicated on the packaging materials.

All vaccine must be discarded after the expiration date

The vial stoppers, syringe plunger stopper and syringe tip cap are not made with natural rubber latex.

Registration Number: 136 52 23874 00

Manufacturer: Merck Sharp & Dohme B.V, Haarlem, The Netherlands

License holder: Merck Sharp & Dohme (Israel-1996) Company Ltd., P.O. Box 7121, Petah-Tikva 49170.

The content of this leaflet was approved by the Ministry of Health in March 2014 and updated according to

the guidelines of the Ministry of Health in April 2018.