ROTATEQ (ROTAVIRUS VACCINE LIVE ORAL PENTAVALENT)

Israel - English - Ministry of Health

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Active ingredient:
ROTAVIRUS G1 REASSORTANT; ROTAVIRUS G2 REASSORTANT; ROTAVIRUS G3 REASSORTANT; ROTAVIRUS G4 REASSORTANT; ROTAVIRUS P1 REASSORTANT
Available from:
MERCK SHARP & DOHME ISRAEL LTD
ATC code:
J07BH
Pharmaceutical form:
ORAL SOLUTION
Composition:
ROTAVIRUS P1 REASSORTANT 2.3 X10 ^6 IU/DOSE; ROTAVIRUS G2 REASSORTANT 2.8 X10 ^6 IU/DOSE; ROTAVIRUS G4 REASSORTANT 2.0 X10^ 6 IU/DOSE; ROTAVIRUS G3 REASSORTANT 2.2 X10 ^6 IU/DOSE; ROTAVIRUS G1 REASSORTANT 2.2 X10 ^6 IU/DOSE
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
MERCK SHARP & DOHME CORP., USA
Therapeutic group:
ROTA VIRUS DIARRHEA VACCINES
Therapeutic indications:
RotaTeq is indicated for the prevention of rotavirus gastroenteritis in infants and children caused by types G1, G2, G3, G4, and G9 when administered as a 3-dose series to infants between the ages of 6 to 32 weeks. The first dose of RotaTeq should be administered between 6 and 12 weeks of age
Authorization number:
136 76 31569 00
Authorization date:
2012-05-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

25-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

25-01-2021

ודי לע רשואו קדבנ ונכותו תואירבה דרשמ י"ע עבקנ הז ןולע טמרופ

ב

טסוגוא

2013

ןכרצל ןולע

קטהטור

P

הטורה ףיגנ דגנ ,יכרע שמח ,ימופ ,יח ןוסיח

ארק י/

תא ,תוריהזב הזה עדימה

מ תחא לכ לבקמ ךדליש ינפל תונמ

יבגל עדימהש הרקמל ,ןוסיחה .הנתשה ןוסיחה

ל קקדזי ךדלי

ונמ .םישדוח רפסמ לש הפוקת ינפ לע ןוסיחה לש ת

אוה ןולעה עדימ לש םוכיס

םייוסמ

יבגל ךדלי לש אפורה םע החישל ףילחת הווהמ וניאו קטהטור

תווצה וא יאופרה .יאופרה םוחתב םייעוצקמ םישנאל בתכנה רתוי אלמ עדימ ךל תתל לוכי רשא ,

?קטהטור לש םיביכרמה םהמ

:ליעפ ביכרמ

םייח םינז

) הטורה ףיגנ לש

G1, G2, G3, G4

:םיליעפ יתלב םיביכרמ

Sucrose,

sodium

citrate,

sodium

phosphate

monobasic

monohydrate,

sodium

hydroxide, polysorbate 80 and also fetal bovine serum

יקלח

porcine circovirus

ףיגנ קיבדמה

םיריזח

םיגוסמ

טטורב ואצמנ ה ףיגנ .ק

porcine

circovirus

גוסמ

(PCV-1)

ה ףיגנו

porcine circovirus

גוסמ

(PCV-2)

םיעודי םניא .םדא ינבב הלחמל םימרוגכ

הטור והמ ?קט

קטהטור

.םידליב הטורה ףיגנב םוהיז תעינמל רזועה ימופ ןוסיח וניה

ב םוהיז לוכי הטורה ףיגנ ולע רשא ,םילושלשו תואקה ,םוח םורגל ) ףוג ילזונ ןדבאל ליבוהלו םירומח תויהל םיל תושבייתה

.םידליהמ קלח לצא תוומ וליפאו ,םיזופשא הטור ןוסיחה קט יושע

לכ לע אלמ ןפואב ןגהל אל ב קבדנ רבכ ךדליו הדימבו ,ןוסיח ולביקש םידליה ףיגנ .ול רוזעי אל ןוסיחה ,

יילע המ

ל

ו

אפורל רמ

יאופרה תווצל וא

לבקמ ידליש ינפל

הטור ?קט

רומא י/

אפורל

ךלש

יאופרה תווצל וא

:ךדלי םא

םוח .םוח םע הלחמב הלוח

לק .ןוסיחה ןתמ תא תוחדל הביס וניא ,ומצעלשכ ןוניצ וא

.איקמ וא לושלשמ לבוס

לקשמב הלוע וניא

וא

.יופצכ לדג וניא

מ לבוס הערפה איהשלכ .םדב

מ לבוס גוס לכ .ןטרס לש והש

השלח ןוסיח תכרעמ לעב וניה

סדייא ללוכ) הלחממ האצותכ

לבקמ

תולולע רשא תופורת לטונ וא לופיט

םינונימ ןוגכ) ולש ןוסיחה תכרעמ תא שילחהל ךלהמב לביקש וא (םידיאורטס לש םיהובג

.םד ירצומ וא םד יוריע םינורחאה םימיה

.ןטב חותינ רבע וא המיסחמ לבסש וא ,לוכיעה תכרעמב תויעב םע דלונ

גמב וניה רחא םדא לכ וא החפשמ ןב םע בורק ע

ררוגתמה

תיבב

מ לבוסהו ןוסיח תכרעמ ,השלח

ןוגכ םדא

לבוס

רשא תופורת לטונה םדא וא ןטרסמ תושילחמ

.ןוסיחה תכרעמ תא

? תעדל ךילע ףסונ בושח עדימ הזיא

לע ןוסיחה רושיא זאמ

תירבה תוצראב תואירבה תויושר ידי

(FDA)

החווד ףיגנ תוטשפתה יחה והשלכ םדא םא יאופרה תווצה שיאל וא ךלש אפורל י/רומא .םינסוחמ םניאש םישנאל ןוס רשא תופורת לטונ וא ןטרס ,השלח ןוסיח תכרעממ לבוס ךתיבב לע ,ןוסיחה תכרעמ תא תושילחמ תופלחה רחאל םיידי ץוחרל ץלמומ .ףסונ עדימ קפסל ולכוי יאופרה תווצה שיא וא אפורהש תנמ נמל םילותיח לש .ןוסיחה ףיגנ תוטשפתה תעי

הטור לבקל רוסא ימל ?קט

תתל ןיא קטהטור םידליל

.ןוסיחה לש הנמ תלבק רחאל תיגרלא הבוגת וחתיפ

.ןוסיחה יביכרממ והשלכ ביכרמל םייגרלא תמישר

םיביכרמ ב תטרופמ תליחת

ןולע

.הז

מ םילבוסה רומח בלושמ ינוסיח רסוח תלחמ

(SCID)

ולבסש

רבעב

תולשפתהמ

,יעמה תמיסח לש גוס

יעמ םי

ןהמ הטור לש תויורשפאה יאוולה תועפות ?קט

צופנה יאוולה תועפות הטור תליטנ רחאל וחוודש רתויב תו ,םוח ,תואקה ,םילושלש ויה קט תלזנ

םיפוצפצ ,ןורג באכ

המישנב .ןזואב םוהיזו ,לועיש וא

םא ,דימ םילוח תיב לש ןוימ רדחל וא ךדלי לש אפורל י/הנפ תויעבהמ תחא לכמ לבוס ךדלי ש ןוויכ ,הנורחאה הנמה זאמ תועובש רפסמ ורבע םא םג ,קטהטור תלבק רחאל תואבה ולא תולולע

) יעמה תולשפתה תארקנה ,תיניצר היעבל םינמיס תויהל

intussusception

הרומח האקה

רומח לושלש

באכ

רומח ןטב

האוצב םד

יעמהמ קלח רשאכ תשחרתמ יעמה תולשפתה .תוועתמ וא םסחנ

לע ןוסיחה רושיא זאמ

תירבה תוצראב תואירבה תויושר ידי

(FDA)

ולבקתה

לע םיחוויד יעמה תולשפתה

קטהטור תלבק רחאל תוקוניתב לע ,

םינוסיחב יאוול תועפות חווידל תכרעמ ידי

(VAERS)

יעמה תולשפתה

םידליהמ קלח לצא .ןוסיחה רחאל תועובש םיתעלו םימי התרק שרדנ

האצותכ תוומ .וז היעבב לופיטל דחוימ ןקוחב ךרוצ היהש וא םייעמה לש חותינ ,זופשא .ןכ םג הרק יעמה תולשפתהמ

יעמה תולשפתה ירקמב הילע הארה קטהטור רושיא רחאל םייקתהש רקחמ

ךלהמב

םימיה קטהטור לש הנושארה הנמה רחאלש ב דחוימב ךא ,

.םינושארה םימיה

ופסונ יאוול תועפות תוללוכ וחוודש ת

םיישק ,הפהו םינפה לש תוחיפנ לולכלו תורומח תויהל תולולע רשא ,תויגרלא תועפות תלרח ,םיפוצפצ ,המישנב

תירוע החירפ וא/ו ,(רועב תיגרלא הבוגת) ו ;

יקאסאווק תלחמ

ש יניצר בצמ) םילוכי םינימסתה ;בלה לע עיפשהל לולע

,םוח לולכל םדוא ,תומודא םייניע ,החירפ ,הפב תוחופנ תוטולב הדימבו ,םיילגרבו םיידיב תוחיפנ , .(תורקל לולע תוומ ,םילפוטמ אלו

רוצ י/

יאוול תעפות וא ךתוא הגיאדמה יאוול תעפות לכ שי ךדליל םא דימ ךלש אפורה םע רשק .הרימחמש

הלא ןניא

לכ הטור לש תוירשפאה יאוולה תועפות .קט המ שקבל ךתורשפאב תווצה וא ךלש אפור רה .רתוי האלמ המישר יאופ

.ךלש דליה לש אפורל יאוול תעפות לכ לע חוודל ,ה/דליה לש סופורטופא וא הרוהכ ,ךילע

אל רשאכ םג תורקל םילוכי קטהטורב ןוסיח רחאל יאוול תועפותכ וחווד וא והוז רשא םיעוריא .ןוסיח ןתינ

הטור תתל ןתינ םאה ?םירחא םינוסיח םע קט

הטור לבקל לוכי ךדלי קט

ואב תודלי ינוסיח לכ םע ןמז ות .םירחא

?קטהטור ןתינ דציכ

לבקי ךדלי .הפה ךרד ןתינ ןוסיחה

ליגב ךדלי רשאכ תנתינ הנושארה הנמה .ןוסיחה לש תונמ

דע

תנתינ היינשה הנמה ,תועובש

דע

תנתינ תישילשה הנמהו רתוי רחואמ תועובש

דע

הנמה .היינשה הנמה רחאל תועובש

ליג דע ךדליל ןתניהל הכירצ (תישילשה) הנורחאה

.תועובש

רפסמ טוטרש האר) ךדלי לש ויפ ךותל ןוסיחה תא טחסיו תונידעב ץחלי יאופרה תווצה שיא

תא בוש תתל ןיא ,הרוק רבדהו הדימב .ולוכ תא וא ןוסיחהמ קלח הצוחה קוריל לולע ךדלי .רוקיב ותואב ןוסיחה

רפסמ טוטרש

ושעל יילע המ הטור לש הנמ ספספמ ידליו הדימב ת ?קט

לכ

ליגל ועיגה דע ךדליל ןתניהל תוכירצ ןוסיחה לש תונמה

ךלש יאופרה תווצה שיא .תועובש םא .הלא שגפמ ינמז לע רומשל בושח .תואבה תונמה תא לבקל עיגהל ךירצ ךדלי יתמ ךל דיגי לוכי ךניאו הדימב וא תחכש ה/

נש ןמזב עיגהל ץעייתה ,עבק י/

.יאופרה תווצה שיא םע

הטורל עגונב תעדל יילע דוע המ ?קט

עגונב תוששח וא ןהשלכ תולאש ךל שי םא .ןוסיחה יבגל םיוסמ עדימ לש םוכיס ןתונ הז ןולע רבד ,קטהטורל י/

.יאופרה תווצה שיא םע

דבלב םשרמ תפורת

:הנסחא

ןסחאל שי רוריקב ליבוהלו לש הרוטרפמטב ,

2-8ºC

םדקהב קטטורב שמתשהל שי .רוא ינפמ ןגהל שי .ררקמהמ ותאצוה רחאל ירשפאה

:הפורתה םושיר רפסמ

136.76.31569.00

ןרצי קרמ : ,.פרוק םהודו פראש טסוו

ב"הרא ,הינבליסנפ ,טניופ

:םושירה לעב

ש קרמ

לארשי) םהודו פר

1996

.ד.ת ,מ"עב (

7121

,הוקת חתפ ,

49170

The format of this leaflet was determined by the Ministry of Health and

its content was checked and approved in August 2013

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

RotaTeq safely and effectively. See full prescribing information

for RotaTeq.

RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent)

Oral Solution

Initial U.S. Approval: 2006

----------------------------RECENT MAJOR CHANGES--------------------------

Warnings and Precautions

Managing Allergic Reactions (5.1)

12/2012

Intussusception (5.3)

06/2013

----------------------------INDICATIONS AND USAGE--------------------------

RotaTeq

is indicated for the prevention of rotavirus gastroenteritis

caused by the G1, G2, G3 and G4 serotypes contained in the vaccine.

RotaTeq is approved for use in infants 6 weeks to 32 weeks of age.

----------------------DOSAGE AND ADMINISTRATION-----------------------

FOR ORAL USE ONLY. NOT FOR INJECTION. (2)

The vaccination series consists of three ready-to-use liquid doses

of RotaTeq administered orally starting at 6 to 12 weeks of age,

with

subsequent

doses

administered

10-week

intervals. The third dose should not be given after 32 weeks of

age. (2)

---------------------DOSAGE FORMS AND STRENGTHS--------------------

2 mL solution for oral administration of 5 live human-bovine reassortant

rotaviruses which contains a minimum of 2.0 – 2.8 x 10

infectious

units (IU) per reassortant dose, depending on the serotype, and not

greater than 116 x 10

IU per aggregate dose. (3)

-------------------------------CONTRAINDICATIONS-----------------------------

A demonstrated history of hypersensitivity to the vaccine or any

component of the vaccine. (4.1)

History of Severe Combined Immunodeficiency Disease (SCID).

(4.2) (6.2)

History of intussusception. (4.3)

-----------------------WARNINGS AND PRECAUTIONS-----------------------

safety

efficacy

data

available

from

clinical

trials

regarding

administration

RotaTeq

infants

potentially immunocompromised (e.g., HIV/AIDS). (5.2)

post-marketing

study,

cases

intussusception

were

observed in temporal association within 21 days following the first

dose of RotaTeq, with a clustering of cases in the first 7 days.

(5.3, 6.2)

No safety or efficacy data are available for the administration of

RotaTeq to infants with a history of gastrointestinal disorders

(e.g., active acute gastrointestinal illness, chronic diarrhea, failure

thrive,

history

congenital

abdominal

disorders,

abdominal surgery). (5.4)

Vaccine

virus

transmission

from

vaccine

recipient

non-

vaccinated contacts has been reported. Caution is advised when

considering whether to administer RotaTeq to individuals with

immunodeficient contacts. (5.5)

------------------------------ADVERSE REACTIONS-----------------------------

Most common adverse events included diarrhea, vomiting, irritability,

otitis media, nasopharyngitis, and bronchospasm. (6.1)

-----------------------USE IN SPECIFIC POPULATIONS----------------------

Pediatric Use: Safety and efficacy have not been established in infants

less than 6 weeks of age or greater than 32 weeks of age. Data are

available from clinical studies to support the use of RotaTeq in:

Pre-term infants according to their age in weeks since birth.

Infants with controlled gastroesophageal reflux disease. (8.4)

See 17 for PATIENT COUNSELING INFORMATION and approved

patient labeling.

Revised 06/2013

_________________________________________________________________________________________________________________________

FULL PRESCRIBING INFORMATION: CONTENTS*

1

INDICATIONS AND USAGE

2

DOSAGE AND ADMINISTRATION

Use with Other Vaccines

Instructions for Use

3

DOSAGE FORMS AND STRENGTHS

4

CONTRAINDICATIONS

4.1 Hypersensitivity

4.2 Severe Combined Immunodeficiency Disease

4.3 History of Intussusception

5

WARNINGS AND PRECAUTIONS

5.1 Managing Allergic Reactions

5.2 Immunocompromised Populations

Intussusception

Gastrointestinal Illness

Shedding and Transmission

Febrile Illness

Incomplete Regimen

Limitations of Vaccine Effectiveness

Post-Exposure Prophylaxis

6

ADVERSE REACTIONS

Clinical Studies Experience

Post-Marketing Experience

7

DRUG INTERACTIONS

Concomitant Vaccine Administration

8

USE IN SPECIFIC POPULATIONS

Pregnancy

Pediatric Use

10

OVERDOSAGE

11

DESCRIPTION

12

CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

13

NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis,

Mutagenesis,

Impairment

Fertility

14

CLINICAL STUDIES

14.1 Rotavirus Efficacy and Safety Trial

14.2 Study 007

14.3 Multiple Rotavirus Seasons

14.4 Rotavirus Gastroenteritis Regardless of Serotype

14.5 Rotavirus Gastroenteritis by Serotype

14.6 Immunogenicity

15

REFERENCES

16

HOW SUPPLIED/STORAGE AND HANDLING

16.1 Storage and Handling

17

PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing

information are not listed.

Copyright © 2006, 2007, 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.,

Whitehouse Station, NJ, USA All Rights Reserved

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

RotaTeq

is indicated for the prevention of rotavirus gastroenteritis in infants and children caused by

the serotypes G1, G2, G3, and G4 when administered as a 3-dose series to infants between the ages of

6 to 32 weeks. The first dose of RotaTeq should be administered between 6 and 12 weeks of age. [see

Dosage and Administration (2)].

2 DOSAGE AND ADMINISTRATION

FOR ORAL USE ONLY. NOT FOR INJECTION.

The vaccination series consists of three ready-to-use liquid doses of RotaTeq administered orally

starting at 6 to 12 weeks of age, with the subsequent doses administered at 4- to 10-week intervals. The

third dose should not be given after 32 weeks of age [see Clinical Studies (14)].

There are no restrictions on the infant’s consumption of food or liquid, including breast milk, either

before or after vaccination with RotaTeq.

Do not mix the RotaTeq vaccine with any other vaccines or solutions. Do not reconstitute or dilute [see

Dosage and Administration (2.2)].

For storage instructions [see How Supplied/Storage and Handling (16.1)].

Each dose is supplied in a container consisting of a squeezable plastic, dosing tube with a twist-off

cap, allowing for direct oral administration. The dosing tube is contained in a pouch [see Dosage and

Administration (2.2)].

2.1 Use with Other Vaccines

In clinical trials, RotaTeq was administered concomitantly with other licensed pediatric vaccines [see

Adverse Reactions (6.1), Drug Interactions (7.1), and Clinical Studies (14)].

2.2 Instructions for Use

To administer the vaccine:

Tear open the pouch and remove the dosing tube.

Clear the fluid from the dispensing tip by holding tube vertically

and tapping cap.

Open the dosing tube in 2 easy motions:

Puncture the dispensing tip by screwing cap clockwise

until it becomes tight.

Remove cap by turning it counterclockwise.

Administer dose by gently squeezing liquid into infant's mouth

toward the inner cheek until dosing tube is empty. (A residual drop

may remain in the tip of the tube.)

If for any reason an incomplete dose is administered (e.g., infant

spits or regurgitates the vaccine), a replacement dose is not

recommended, since such dosing was not studied in the clinical

trials. The infant should continue to receive any remaining doses

in the recommended series.

Discard the empty tube and cap in approved biological waste

containers according to local regulations.

3 DOSAGE FORMS AND STRENGTHS

RotaTeq, 2 mL for oral use, is a ready-to-use solution of live reassortant rotaviruses, containing G1, G2,

G3, G4 and P1A[8] which contains a minimum of 2.0 – 2.8 x 10

infectious units (IU) per individual

reassortant dose, depending on the serotype, and not greater than 116 x 10

IU per aggregate dose.

Each dose is supplied in a container consisting of a squeezable plastic dosing tube with a twist-off cap,

allowing for direct oral administration. The dosing tube is contained in a pouch.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

A demonstrated history of hypersensitivity to any component of the vaccine.

Infants who develop symptoms suggestive of hypersensitivity after receiving a dose of RotaTeq should

not receive further doses of RotaTeq.

4.2 Severe Combined Immunodeficiency Disease

Infants with Severe Combined Immunodeficiency Disease (SCID) should not receive RotaTeq. Post-

marketing reports of gastroenteritis, including severe diarrhea and prolonged shedding of vaccine virus,

have been reported in infants who were administered RotaTeq and later identified as having SCID [see

Adverse Reactions (6.2)].

4.3 History of Intussusception

Infants with a history of intussusception should not receive RotaTeq.

5 WARNINGS AND PRECAUTIONS

5.1

Managing Allergic Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic

reactions following administration of the vaccine.

5.2 Immunocompromised Populations

No safety or efficacy data are available from clinical trials regarding the administration of RotaTeq to

infants who are potentially immunocompromised including:

Infants with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms

affecting the bone marrow or lymphatic system.

Infants on immunosuppressive therapy (including high-dose systemic corticosteroids). RotaTeq may

be administered to infants who are being treated with topical corticosteroids or inhaled steroids.

Infants with primary and acquired immunodeficiency states, including HIV/AIDS or other clinical

manifestations of infection with human immunodeficiency viruses; cellular immune deficiencies; and

hypogammaglobulinemic and dysgammaglobulinemic states. There are insufficient data from the

clinical trials to support administration of RotaTeq to infants with indeterminate HIV status who are

born to mothers with HIV/AIDS.

Infants who have received a blood transfusion or blood products, including immunoglobulins within

42 days.

Vaccine virus transmission from vaccine recipient to non-vaccinated contacts has been reported [see

Warnings and Precautions (5.5)].

5.3 Intussusception

Following

administration

previously

licensed

live

rhesus

rotavirus

reassortant

vaccine,

increased risk of intussusception was observed.

In a post-marketing observational study in the US cases of intussusception were observed in temporal

association within 21 days following the first dose of RotaTeq, with a clustering of cases in the first 7

days.

[See Adverse Reactions (6.2)]

In worldwide passive post-marketing surveillance, cases of intussusception have been reported in

temporal association with RotaTeq. [See Adverse Reactions (6.2)]

5.4 Gastrointestinal Illness

No safety or efficacy data are available for administration of RotaTeq to infants with a history of

gastrointestinal disorders including infants with active acute gastrointestinal illness, infants with chronic

diarrhea and failure to thrive, and infants with a history of congenital abdominal disorders, and abdominal

surgery. Caution is advised when considering administration of RotaTeq to these infants.

5.5 Shedding and Transmission

Shedding of vaccine virus was evaluated among a subset of subjects in the Rotavirus Efficacy and

Safety Trial (REST) 4 to 6 days after each dose and among all subjects who submitted a stool antigen

rotavirus positive sample at any time. RotaTeq was shed in the stools of 32 of 360 [8.9%, 95% CI (6.2%,

12.3%)] vaccine recipients tested after dose 1; 0 of 249 [0.0%, 95% CI (0.0%, 1.5%)] vaccine recipients

tested after dose 2; and in 1 of 385 [0.3%, 95% CI (<0.1%, 1.4%)] vaccine recipients after dose 3. In

phase 3 studies, shedding was observed as early as 1 day and as late as 15 days after a dose.

Transmission of vaccine virus was not evaluated in phase 3 studies.

Transmission of vaccine virus strains from vaccinees to non-vaccinated contacts has been observed

post-marketing.

The potential risk of transmission of vaccine virus should be weighed against the risk of acquiring and

transmitting natural rotavirus.

Caution is advised when considering whether to administer RotaTeq to individuals with immunodeficient

close contacts such as:

Individuals with malignancies or who are otherwise immunocompromised;

Individuals with primary immunodeficiency; or

Individuals receiving immunosuppressive therapy.

5.6 Febrile Illness

Febrile illness may be reason for delaying use of RotaTeq except when, in the opinion of the

physician, withholding the vaccine entails a greater risk. Low-grade fever (<100.5°F [38.1°C]) itself and

mild upper respiratory infection do not preclude vaccination with RotaTeq.

5.7 Incomplete Regimen

The clinical studies were not designed to assess the level of protection provided by only one or two

doses of RotaTeq.

5.8 Limitations of Vaccine Effectiveness

RotaTeq may not protect all vaccine recipients against rotavirus.

5.9 Post-Exposure Prophylaxis

No clinical data are available for RotaTeq when administered after exposure to rotavirus.

6 ADVERSE REACTIONS

6.1

Clinical Studies Experience

71,725 infants were evaluated in 3 placebo-controlled clinical trials including 36,165 infants in the

group that received RotaTeq and 35,560 infants in the group that received placebo. Parents/guardians

were contacted on days 7, 14, and 42 after each dose regarding intussusception and any other serious

adverse events. The racial distribution was as follows: White (69% in both groups); Hispanic-American

(14% in both groups); Black (8% in both groups); Multiracial (5% in both groups); Asian (2% in both

groups); Native American (RotaTeq 2%, placebo 1%); and Other (<1% in both groups). The gender

distribution was 51% male and 49% female in both vaccination groups.

Because clinical trials are conducted under conditions that may not be typical of those observed in

clinical practice, the adverse reaction rates presented below may not be reflective of those observed in

clinical practice.

Serious Adverse Events

Serious adverse events occurred in 2.4% of recipients of RotaTeq when compared to 2.6% of placebo

recipients within the 42-day period of a dose in the phase 3 clinical studies of RotaTeq. The most

frequently reported serious adverse events for RotaTeq compared to placebo were:

bronchiolitis

(0.6% RotaTeq vs. 0.7% Placebo),

gastroenteritis

(0.2% RotaTeq vs. 0.3% Placebo),

pneumonia

(0.2% RotaTeq vs. 0.2% Placebo),

fever

(0.1% RotaTeq vs. 0.1% Placebo), and

urinary tract infection

(0.1% RotaTeq vs. 0.1% Placebo).

Deaths

Across the clinical studies, 52 deaths were reported. There were 25 deaths in the RotaTeq recipients

compared to 27 deaths in the placebo recipients. The most commonly reported cause of death was

sudden infant death syndrome, which was observed in 8 recipients of RotaTeq and 9 placebo recipients.

Intussusception

REST,

34,837

vaccine

recipients

34,788

placebo

recipients

were

monitored

active

surveillance to identify potential cases of intussusception at 7, 14, and 42 days after each dose, and

every 6 weeks thereafter for 1 year after the first dose.

For the primary safety outcome, cases of intussusception occurring within 42 days of any dose, there

were 6 cases among RotaTeq recipients and 5 cases among placebo recipients (see Table 1). The data

did not suggest an increased risk of intussusception relative to placebo.

Table 1

Confirmed cases of intussusception in recipients of RotaTeq as compared with placebo recipients during REST

RotaTeq

(n=34,837)

Placebo

(n=34,788)

Confirmed intussusception cases within 42 days

of any dose

Relative risk (95% CI)

1.6 (0.4, 6.4)

Confirmed intussusception cases within 365

days of dose 1

Relative risk (95% CI)

0.9 (0.4, 1.9)

Relative risk and 95% confidence interval based upon group sequential design stopping criteria

employed in REST.

Among vaccine recipients, there were no confirmed cases of intussusception within the 42-day period

after the first dose, which was the period of highest risk for the rhesus rotavirus-based product (see Table

Table 2

Intussusception cases by day range in relation to dose in REST

Dose 1

Dose 2

Dose 3

Any Dose

Day Range

RotaTeq

Placebo

RotaTeq

Placebo

RotaTeq

Placebo

RotaTeq

Placebo

1-14

1-21

1-42

All of the children who developed intussusception recovered without sequelae with the

exception of a 9-month-old male who developed intussusception 98 days after dose 3 and

died of post-operative sepsis. There was a single case of intussusception among 2,470

recipients of RotaTeq in a 7-month-old male in the phase 1 and 2 studies (716 placebo

recipients).

Hematochezia

Hematochezia reported as an adverse experience occurred in 0.6% (39/6,130) of vaccine and 0.6%

(34/5,560) of placebo recipients within 42 days of any dose. Hematochezia reported as a serious adverse

experience occurred in <0.1% (4/36,150) of vaccine and <0.1% (7/35,536) of placebo recipients within 42

days of any dose.

Seizures

All seizures reported in the phase 3 trials of RotaTeq (by vaccination group and interval after dose) are

shown in Table 3.

Table 3

Seizures reported by day range in relation to any dose in the phase 3 trials of RotaTeq

Day range

1-14

1-42

RotaTeq

Placebo

Seizures reported as serious adverse experiences occurred in <0.1% (27/36,150) of vaccine and

<0.1% (18/35,536) of placebo recipients (not significant). Ten febrile seizures were reported as serious

adverse experiences, 5 were observed in vaccine recipients and 5 in placebo recipients.

Kawasaki Disease

In the phase 3 clinical trials, infants were followed for up to 42 days of vaccine dose. Kawasaki disease

was reported in 5 of 36,150 vaccine recipients and in 1 of 35,536 placebo recipients with unadjusted

relative risk 4.9 (95% CI 0.6, 239.1).

Most Common Adverse Events

Solicited Adverse Events

Detailed safety information was collected from 11,711 infants (6,138 recipients of RotaTeq) which

included a subset of subjects in REST and all subjects from Studies 007 and 009 (Detailed Safety

Cohort). A Vaccination Report Card was used by parents/guardians to record the child’s temperature and

any episodes of diarrhea and vomiting on a daily basis during the first week following each vaccination.

Table 4 summarizes the frequencies of these adverse events and irritability.

Table 4

Solicited adverse experiences within the first week after doses 1, 2, and 3 (Detailed Safety Cohort)

Adverse experience

Dose 1

Dose 2

Dose 3

RotaTeq

Placebo

RotaTeq

Placebo

RotaTeq

Placebo

Elevated temperature*

n=5,616

17.1%

n=5,077

16.2%

n=5,215

20.0%

n=4,725

19.4%

n=4,865

18.2%

n=4,382

17.6%

n=6,130

n=5,560

n=5,703

n=5,173

n=5,496

n=4,989

Vomiting

6.7%

5.4%

5.0%

4.4%

3.6%

3.2%

Diarrhea

10.4%

9.1%

8.6%

6.4%

6.1%

5.4%

Irritability

7.1%

7.1%

6.0%

6.5%

4.3%

4.5%

*Temperature ≥100.5°F [38.1°C] rectal equivalent obtained by adding 1 degree F to otic and oral temperatures and 2 degrees F to axillary

temperatures

Other Adverse Events

Parents/guardians of the 11,711 infants were also asked to report the presence of other events on the

Vaccination Report Card for 42 days after each dose.

Fever was observed at similar rates in vaccine (N=6,138) and placebo (N=5,573) recipients (42.6% vs.

42.8%). Adverse events that occurred at a statistically higher incidence (i.e., 2-sided p-value <0.05) within

the 42 days of any dose among recipients of RotaTeq as compared with placebo recipients are shown in

Table 5.

Table 5

Adverse events that occurred at a statistically higher incidence within 42 days of any dose among recipients of RotaTeq as compared with placebo

recipients

Adverse event

RotaTeq

N=6,138

Placebo

N=5,573

n (%)

n (%)

Diarrhea

1,479 (24.1%)

1,186 (21.3%)

Vomiting

929 (15.2%)

758 (13.6%)

Otitis media

887 (14.5%)

724 (13.0%)

Nasopharyngitis

422 (6.9%)

325 (5.8%)

Bronchospasm

66 (1.1%)

40 (0.7%)

Safety in Pre-Term Infants

RotaTeq or placebo was administered to 2,070 pre-term infants (25 to 36 weeks gestational age,

median 34 weeks) according to their age in weeks since birth in REST. All pre-term infants were followed

for serious adverse experiences; a subset of 308 infants was monitored for all adverse experiences.

There were 4 deaths throughout the study, 2 among vaccine recipients (1 SIDS and 1 motor vehicle

accident) and 2 among placebo recipients (1 SIDS and 1 unknown cause). No cases of intussusception

were reported. Serious adverse experiences occurred in 5.5% of vaccine and 5.8% of placebo recipients.

The most common serious adverse experience was bronchiolitis, which occurred in 1.4% of vaccine and

2.0% of placebo recipients. Parents/guardians were asked to record the child’s temperature and any

episodes of vomiting and diarrhea daily for the first week following vaccination. The frequencies of these

adverse experiences and irritability within the week after dose 1 are summarized in Table 6.

Table 6

Solicited adverse experiences within the first week of doses 1, 2, and 3 among pre-term infants

Dose 1

Dose 2

Dose 3

Adverse event

RotaTeq

Placebo

RotaTeq

Placebo

RotaTeq

Placebo

N=127

N=133

N=124

N=121

N=115

N=108

Elevated temperature*

18.1%

17.3%

25.0%

28.1%

14.8%

20.4%

N=154

N=154

N=137

N=137

N=135

N=129

Vomiting

5.8%

7.8%

2.9%

2.2%

4.4%

4.7%

Diarrhea

6.5%

5.8%

7.3%

7.3%

3.7%

3.9%

Irritability

3.9%

5.2%

2.9%

4.4%

8.1%

5.4%

*Temperature ≥100.5°F [38.1°C] rectal equivalent obtained by adding 1 degree F to otic and oral temperatures and 2 degrees F to axillary

temperatures

6.2 Post-Marketing Experience

The following adverse events have been identified during post-approval use of RotaTeq from reports

to the Vaccine Adverse Event Reporting System (VAERS).

Reporting of adverse events following immunization to VAERS is voluntary, and the number of doses

of vaccine administered is not known; therefore, it is not always possible to reliably estimate the adverse

event frequency or establish a causal relationship to vaccine exposure using VAERS data.

In post-marketing experience, the following adverse events have been reported following the use of

RotaTeq:

Immune system disorders:

Anaphylactic reaction

Gastrointestinal disorders:

Intussusception (including death)

Hematochezia

Gastroenteritis

with

vaccine

viral

shedding

infants

with

Severe

Combined

Immunodeficiency

Disease (SCID)

Skin and subcutaneous tissue disorders:

Urticaria

Angioedema

Infections and infestations

Kawasaki disease

Transmission of vaccine virus strains from vaccine recipient to non-vaccinated contacts.

Post-Marketing Observational Safety Surveillance Studies

The temporal association between vaccination with RotaTeq and intussusception was evaluated in the

Post-licensure Rapid Immunization Safety Monitoring (PRISM) program

, an electronic active surveillance

program comprised of 3 US health insurance plans.

More than 1.2 million RotaTeq vaccinations (507,000 of which were first doses) administered to infants

5 through 36 weeks of age were evaluated. From 2004 through 2011, potential cases of intussusception

in either the inpatient or emergency department setting and vaccine exposures were identified through

electronic procedure and diagnosis codes. Medical records were reviewed to confirm intussusception and

rotavirus vaccination status.

The risk of intussusception was assessed using self-controlled risk interval and cohort designs, with

adjustment for age. Risk windows of 1-7 and 1-21 days were evaluated. Cases of intussusception were

observed in temporal association within 21 days following the first dose of RotaTeq, with a clustering of

cases in the first 7 days. Based on the results, approximately 1 to 1.5 excess cases of intussusception

occur per 100,000 vaccinated US infants within 21 days following the first dose of RotaTeq. In the first

year of life, the background rate of intussusception hospitalizations in the US has been estimated to be

approximately 34 per 100,000 infants.

In an earlier prospective post-marketing observational cohort study conducted using a large US

medical claims database, the risks of intussusception or Kawasaki disease resulting in emergency

department visits or hospitalizations during the 30 days following any dose of vaccine were analyzed

among 85,150 infants receiving one or more doses of RotaTeq from February 2006 through March 2009.

Medical charts were reviewed to confirm these diagnoses.

Evaluation included concurrent (n = 62,617) and historical (n=100,000 from 2001-2005) control groups of

infants who received diphtheria, tetanus and acellular pertussis vaccine (DTaP) but not RotaTeq.

Confirmed intussusception cases in the RotaTeq group were compared with those in the concurrent

DTaP control group and in the historical control group. The data were analyzed post dose 1 and post any

dose, in both 7 day and 30 day risk windows. A statistically significant increased risk of intussusception

after RotaTeq vaccination was not observed.

One confirmed case of Kawasaki disease (23 days post-dose 3) was identified among infants

vaccinated with RotaTeq and one confirmed case of Kawasaki disease (22 days post-dose 2) was

identified among concurrent DTaP controls (relative risk = 0.7; 95% CI: 0.01-55.56).

In addition, general safety was monitored by electronic search of the automated records database for

all emergency department visits and hospitalizations in the 30-day period after each dose of RotaTeq

compared with: 1) days 31-60 after each dose of RotaTeq (self-matched controls) and 2) the 30-day

period after each dose of DTaP vaccine (historical control subset from 2004-2005, n=40,000). In safety

analyses which evaluated multiple follow-up windows after vaccination (days: 0-7, 1-7, 8-14 and 0-30), no

safety concerns were identified for infants vaccinated with RotaTeq when compared with self-matched

controls and the historical control subset.

Reporting Adverse Events

Parents or guardians should be instructed to report any adverse reactions to their health care provider.

7 DRUG INTERACTIONS

Immunosuppressive therapies including irradiation, antimetabolites, alkylating agents, cytotoxic drugs

and corticosteroids (used in greater than physiologic doses), may reduce the immune response to

vaccines.

7.1 Concomitant Vaccine Administration

In clinical trials, RotaTeq was administered concomitantly with diphtheria and tetanus toxoids and

acellular pertussis (DTaP), inactivated poliovirus vaccine (IPV), H. influenzae type b conjugate (Hib),

hepatitis B vaccine, and pneumococcal conjugate vaccine [see Clinical Studies (14)]. The safety data

available are in the ADVERSE REACTIONS section [see Adverse Reactions (6.1)].

There was no evidence for reduced antibody responses to the vaccines that were concomitantly

administered with RotaTeq.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with RotaTeq. It is also

not known whether RotaTeq can cause fetal harm when administered to a pregnant woman or can affect

reproduction capacity. RotaTeq is not indicated in women of child-bearing age and should not be

administered to pregnant females.

8.4 Pediatric Use

Safety and efficacy have not been established in infants less than 6 weeks of age or greater than 32

weeks of age.

Data are available from clinical studies to support the use of RotaTeq in pre-term infants according to

their age in weeks since birth [see Adverse Reactions (6.1)].

Data are available from clinical studies to support the use of RotaTeq in infants with controlled

gastroesophageal reflux disease.

10

OVERDOSAGE

There have been post-marketing reports of infants who received more than one dose or a replacement

dose of RotaTeq after regurgitation [see Dosage and Administration (2.2)]. In limited post-marketing

experience of reported overdosage, the adverse events reported after incorrect administration of higher

than recommended doses of RotaTeq were similar to adverse events observed with the approved dosage

and schedule.

11 DESCRIPTION

RotaTeq is a live, oral pentavalent vaccine that contains 5 live reassortant rotaviruses. The rotavirus

parent strains of the reassortants were isolated from human and bovine hosts. Four reassortant

rotaviruses express one of the outer capsid proteins (G1, G2, G3, or G4) from the human rotavirus parent

strain and the attachment protein (serotype P7) from the bovine rotavirus parent strain. The fifth

reassortant virus expresses the attachment protein, P1A (genotype P[8]), herein referred to as serotype

P1A[8], from the human rotavirus parent strain and the outer capsid protein of serotype G6 from the

bovine rotavirus parent strain (see Table 7).

Table 7

Name of

Reassortant

Human Rotavirus Parent

Strains

and Outer Surface Protein

Compositions

Bovine Rotavirus Parent

Strain and Outer Surface

Protein Composition

Reassortant Outer Surface

Protein Composition

(Human Rotavirus Component

in Bold)

Minimum Dose Levels

infectious units)

WI79 – G1P1A[8]

WC3 - G6, P7[5]

G1P7[5]

SC2 – G2P2[6]

G2P7[5]

WI78 – G3P1A[8]

G3P7[5]

BrB – G4P2[6]

G4P7[5]

P1A[8]

WI79 – G1P1A[8]

G6P1A[8]

The reassortants are propagated in Vero cells using standard cell culture techniques in the absence of

antifungal agents.

The reassortants are suspended in a buffered stabilizer solution. Each vaccine dose contains sucrose,

sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80, cell

culture media, and trace amounts of fetal bovine serum. RotaTeq contains no preservatives.

In the manufacturing process for RotaTeq, a porcine-derived material is used. DNA from porcine

circoviruses (PCV) 1 and 2 has been detected in RotaTeq. PCV-1 and PCV-2 are not known to cause

disease in humans.

RotaTeq is a pale yellow clear liquid that may have a pink tint.

The plastic dosing tube and cap do not contain latex.

12 CLINICAL PHARMACOLOGY

Rotavirus is a leading cause of severe acute gastroenteritis in infants and young children, with over

95% of these children infected by the time they are 5 years old.

The most severe cases occur among

infants and young children between 6 months and 24 months of age.

12.1 Mechanism of Action

The exact immunologic mechanism by which RotaTeq protects against rotavirus gastroenteritis is

unknown [see Clinical Studies (14.6)]. RotaTeq is a live viral vaccine that replicates in the small intestine

and induces immunity.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

RotaTeq has not been evaluated for its carcinogenic or mutagenic potential or its potential to impair

fertility.

14 CLINICAL STUDIES

Overall, 72,324 infants were randomized in 3 placebo-controlled, phase 3 studies conducted in 11

countries on 3 continents. The data demonstrating the efficacy of RotaTeq in preventing rotavirus

gastroenteritis come from 6,983 of these infants from the US (including Navajo and White Mountain

Apache Nations) and Finland who were enrolled in 2 of these studies: REST and Study 007. The third

trial, Study 009, provided clinical evidence supporting the consistency of manufacture and contributed

data to the overall safety evaluation.

The racial distribution of the efficacy subset was as follows: White (RotaTeq 68%, placebo 69%);

Hispanic-American (RotaTeq 10%, placebo 9%); Black (2% in both groups); Multiracial (RotaTeq 4%,

placebo 5%); Asian (<1% in both groups); Native American (RotaTeq 15%, placebo 14%); and Other

(<1% in both groups). The gender distribution was 52% male and 48% female in both vaccination groups.

The efficacy evaluations in these studies included: 1) Prevention of any grade of severity of rotavirus

gastroenteritis; 2) Prevention of severe rotavirus gastroenteritis, as defined by a clinical scoring system;

and 3) Reduction in hospitalizations due to rotavirus gastroenteritis.

The vaccine was given as a three-dose series to healthy infants with the first dose administered

between 6 and 12 weeks of age and followed by two additional doses administered at 4- to 10-week

intervals. The age of infants receiving the third dose was 32 weeks of age or less. Oral polio vaccine

administration

permitted;

however,

other

childhood

vaccines

could

concomitantly

administered. Breast-feeding was permitted in all studies.

The case definition for rotavirus gastroenteritis used to determine vaccine efficacy required that a

subject meet both of the following clinical and laboratory criteria: (1) greater than or equal to 3 watery or

looser-than-normal stools within a 24-hour period and/or forceful vomiting; and (2) rotavirus antigen

detection by enzyme immunoassay (EIA) in a stool specimen taken within 14 days of onset of symptoms.

The severity of rotavirus acute gastroenteritis was determined by a clinical scoring system that took into

account the intensity and duration of symptoms of fever, vomiting, diarrhea, and behavioral changes.

The primary efficacy analyses included cases of rotavirus gastroenteritis caused by serotypes G1, G2,

G3, and G4 that occurred at least 14 days after the third dose through the first rotavirus season post

vaccination.

Analyses were also done to evaluate the efficacy of RotaTeq against rotavirus gastroenteritis caused

by serotypes G1, G2, G3, and G4 at any time following the first dose through the first rotavirus season

postvaccination among infants who received at least one vaccination (Intent-to-treat, ITT).

14.1 Rotavirus Efficacy and Safety Trial

Primary efficacy against any grade of severity of rotavirus gastroenteritis caused by naturally occurring

serotypes G1, G2, G3, or G4 through the first rotavirus season after vaccination was 74.0% (95% CI:

66.8, 79.9) and the ITT efficacy was 60.0% (95% CI: 51.5, 67.1). Primary efficacy against severe rotavirus

gastroenteritis caused by naturally occurring serotypes G1, G2, G3, or G4 through the first rotavirus

season after vaccination was 98.0% (95% CI: 88.3, 100.0), and ITT efficacy was 96.4% (95% CI: 86.2,

99.6). See Table 8.

Table 8

Efficacy of RotaTeq against any grade of severity of and severe* G1-4 rotavirus gastroenteritis through the first

rotavirus season postvaccination in REST

Per Protocol

Intent-to-Treat

RotaTeq

Placebo

RotaTeq

Placebo

Subjects vaccinated

2,834

2,839

2,834

2,839

Gastroenteritis cases

Any grade of severity

Severe*

Efficacy estimate % and (95% confidence interval)

Any grade of severity

74.0

(66.8, 79.9)

60.0

(51.5, 67.1)

Severe*

98.0

(88.3, 100.0)

96.4

(86.2, 99.6)

*Severe gastroenteritis defined by a clinical scoring system based on the intensity and duration of symptoms of fever, vomiting,

diarrhea, and behavioral changes

ITT analysis includes all subjects in the efficacy cohort who received at least one dose of vaccine.

efficacy

RotaTeq

against

severe

disease

also

demonstrated

reduction

hospitalizations for rotavirus gastroenteritis among all subjects enrolled in REST. RotaTeq reduced

hospitalizations for rotavirus gastroenteritis caused by serotypes G1, G2, G3, and G4 through the first two

years after the third dose by 95.8% (95% CI: 90.5, 98.2). The ITT efficacy in reducing hospitalizations

was 94.7% (95% CI: 89.3, 97.3) as shown in Table 9.

Table 9

Efficacy of RotaTeq in reducing G1-4 rotavirus-related hospitalizations in REST

Per Protocol

Intent-to-Treat*

RotaTeq

Placebo

RotaTeq

Placebo

Subjects vaccinated

34,035

34,003

34,035

34,003

Number of hospitalizations

Efficacy estimate % and

(95% confidence interval)

95.8

(90.5, 98.2)

94.7

(89.3, 97.3)

*ITT analysis includes all subjects who received at least one dose of vaccine.

14.2 Study 007

Primary efficacy against any grade of severity of rotavirus gastroenteritis caused by naturally occurring

serotypes G1, G2, G3, or G4 through the first rotavirus season after vaccination was 72.5% (95% CI:

50.6, 85.6) and the ITT efficacy was 58.4% (95% CI: 33.8, 74.5). Primary efficacy against severe rotavirus

gastroenteritis caused by naturally occurring serotypes G1, G2, G3, or G4 through the first rotavirus

season after vaccination was 100% (95% CI: 13.0, 100.0) and ITT efficacy against severe rotavirus

disease was 100% (95% CI: 30.2, 100.0) as shown in Table 10.

Table 10

Efficacy of RotaTeq against any grade of severity of and severe* G1-4 rotavirus gastroenteritis through the first

rotavirus season postvaccination in Study 007

Per Protocol

Intent-to-Treat

RotaTeq

Placebo

RotaTeq

Placebo

Subjects vaccinated

Gastroenteritis cases

Any grade of severity

Severe*

Efficacy estimate % and (95% confidence interval)

Any grade of severity

72.5

(50.6, 85.6)

58.4

(33.8, 74.5)

Severe*

100.0

(13.0, 100.0)

100.0

(30.2, 100.0)

*Severe gastroenteritis defined by a clinical scoring system based on the intensity and duration of symptoms of fever, vomiting,

diarrhea, and behavioral change

ITT analysis includes all subjects in the efficacy cohort who received at least one dose of vaccine.

14.3 Multiple Rotavirus Seasons

The efficacy of RotaTeq through a second rotavirus season was evaluated in a single study (REST).

Efficacy against any grade of severity of rotavirus gastroenteritis caused by rotavirus serotypes G1, G2,

G3, and G4 through the two rotavirus seasons after vaccination was 71.3% (95% CI: 64.7, 76.9). The

efficacy

RotaTeq

preventing

cases

occurring

only

during

second

rotavirus

season

postvaccination was 62.6% (95% CI: 44.3, 75.4). The efficacy of RotaTeq beyond the second season

postvaccination was not evaluated.

14.4 Rotavirus Gastroenteritis Regardless of Serotype

The rotavirus serotypes identified in the efficacy subset of REST and Study 007 were G1P1A[8];

G2P1[4]; G3P1A[8]; G4P1A[8]; and G9P1A[8].

REST,

efficacy

RotaTeq

against

grade

severity

naturally

occurring

rotavirus

gastroenteritis regardless of serotype was 71.8% (95% CI: 64.5, 77.8) and efficacy against severe

rotavirus disease was 98.0% (95% CI: 88.3, 99.9). The ITT efficacy starting at dose 1 was 50.9%

(95% CI: 41.6, 58.9) for any grade of severity of rotavirus disease and was 96.4% (95% CI: 86.3, 99.6) for

severe rotavirus disease.

In Study 007, the primary efficacy of RotaTeq against any grade of severity of rotavirus gastroenteritis

regardless of serotype was 72.7% (95% CI: 51.9, 85.4) and efficacy against severe rotavirus disease was

100% (95% CI: 12.7, 100). The ITT efficacy starting at dose 1 was 48.0% (95% CI: 21.6, 66.1) for any

grade of severity of rotavirus disease and was 100% (95% CI: 30.4, 100.0) for severe rotavirus disease.

14.5 Rotavirus Gastroenteritis by Serotype

The efficacy against any grade of severity of rotavirus gastroenteritis by serotype in the REST efficacy

cohort is shown in Table 11.

Table 11

Serotype-specific efficacy of RotaTeq against any grade of severity of rotavirus gastroenteritis among infants in the REST efficacy cohort through the

first rotavirus season postvaccination (Per Protocol)

Serotype identified by PCR

Number of cases

% Efficacy

(95% Confidence Interval)

RotaTeq

(N=2,834)

Placebo

(N=2,839)

Serotypes present in RotaTeq

G1P1A[8]

74.9 (67.3, 80.9)

G2P1[4]

63.4 (2.6, 88.2)

G3P1A[8]

G4P1A[8]

Serotypes not present in RotaTeq

G9P1A[8]

Unidentified*

N=number vaccinated

NS=not significant

*Includes rotavirus antigen-positive samples in which the specific serotype could not be identified by PCR

In a separate post hoc analysis of health care utilization data from 68,038 infants (RotaTeq 34,035 and

placebo 34,003) in REST, using a case definition that included culture confirmation, hospitalization and

emergency departments visits due to G9P1A[8] rotavirus gastroenteritis were reduced (RotaTeq 0 cases:

placebo 14 cases) by 100% (95% CI: 69.6%, 100.0%).

14.6 Immunogenicity

A relationship between antibody responses to RotaTeq and protection against rotavirus gastroenteritis

has not been established. In phase 3 studies, 92.9% to 100% of 439 recipients of RotaTeq achieved a 3-

fold or more rise in serum anti-rotavirus IgA after a three-dose regimen when compared to 12.3%-20.0%

of 397 placebo recipients.

15 REFERENCES

Murphy TV, Gargiullo PM, Massoudi MS et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med

2001;344:564-572.

Yih WK, Lieu TA, Kulldorff M, et al. Intussusception risk after rotavirus vaccination in US infants. Mini-Sentinel. www.mini-

sentinel.org.

Tate JE, Simonsen L, Viboud C, et al. Trends in intussusception hospitalizations among US infants, 1993-2004: implications for

monitoring the safety of the new rotavirus vaccination program. Pediatrics 2008;121(5):e1125-e1132.

Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory

Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR 2002;51(RR-

2):1-35.

Parashar UD et al. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis 2003;9(5):565-572.

Parashar UD, Holman RC, Clarke MJ, Bresee JS, Glass RI. Hospitalizations associated with rotavirus diarrhea in the United

States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus-specific diagnostic code. J Infect Dis

1998;177:13-7.

16 HOW SUPPLIED/STORAGE AND HANDLING

RotaTeq, 2 mL, a solution for oral use, is a pale yellow clear liquid that may have a pink tint. It is

supplied as follows:

Package of 1 individually pouched single-dose tube.

Package of 10 individually pouched single-dose tubes.

The plastic dosing tube and cap do not contain latex.

16.1 Storage and Handling

Store and transport refrigerated at 2-8°C.

RotaTeq should be administered as soon as possible after

being removed from refrigeration. Protect from light.

RotaTeq should be discarded in approved biological waste containers according to local regulations.

The product must be used before the expiration date.

17 PATIENT COUNSELING INFORMATION

See Approved Patient Labeling (Patient Information).

Parents or guardians should be given a copy of the required vaccine information and be given the

“Patient Information". Parents and/or guardians should be encouraged to read the patient information that

describes the benefits and risks associated with the vaccine and ask any questions they may have during

the visit. [see Warnings and Precautions (5) and Patient Information].

18 MANUFACTURER

Merck Sharp & Dohme Corp., West-Point, Pennsylvania, USA.

19 LICENSE HOLDER

Merck Sharp & Dohme (Israel - 1996) Company Ltd., P.O.B. 7121, Petah-Tikva 49170.

Revised: 06/2013

Printed in USA

USPI-OS-V2601306R020.

העדוה העדוה

לע לע

הרמחה הרמחה

(

(

עדימ עדימ

)תוחיטב )תוחיטב

ךיראת

___

8.7.2013

__

םש

רישכת

תילגנאב

רפסמו

םושירה

ROTATEQ (ROTAVIRUS VACCINE,

LIVE, ORAL, PENTAVALENT) (136 76 31569 00)

םש

לעב

םושירה

MERCK SHARP & DOHME ISRAEL LTD

םייונישה

ןולעב

םינמוסמ

לע

עקר

בוהצ ןולעב ןולעב

ל

ל

אפור אפור תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

HIGHLIGHTS OF

PRESCRIBING

INFORMATION

RECENT MAJOR CHANGES

WARNINGS AND

PRECAUTIONS

Warnings and Precautions

Managing Allergic Reactions (5.1) 12/2012

Intussusception (5.3) 06/2013

post-marketing

study,

cases

intussusception were observed in temporal association

within 21 days following the first dose of RotaTeq, with a

clustering of cases in the first 7 days. (5.3, 6.2)

WARNINGS AND

PRECAUTIONS-

5.1 Managing Allergic Reactions

Appropriate medical treatment and supervision

must be available to manage possible anaphylactic

reactions following administration of the vaccine.

5.3 Intussusception

In a post-marketing observational study in the US

cases of Intussusception were observed in temporal

association within 21 days following the first dose of

RotaTeq, with a clustering of cases in the first 7

days. [See Adverse Reactions (6.2)]

ADVERSE

REACTIONS

-

6.2 Post-Marketing Experience

Immune system disorders: Anaphylactic reaction.

Skin and subcutaneous tissue disorders:

Angioedema

Post-Marketing Observational Safety Surveillance

Studies

The temporal association between vaccination with

RotaTeq and intussusception was evaluated in the

Post-licensure Rapid Immunization Safety

Monitoring (PRISM) program

, an electronic active

surveillance program comprised of 3 US health

insurance plans.

More than 1.2 million RotaTeq vaccinations

(507,000 of which were first doses) administered to

infants 5 through 36 weeks of age were evaluated.

From 2004 through 2011, potential cases of

intussusception in either the inpatient or emergency

department setting and vaccine exposures were

identified through electronic procedure and

diagnosis codes. Medical records were reviewed to

confirm intussusception and rotavirus vaccination

Page 1 of 3

status.

The risk of intussusception was assessed using

self-controlled risk interval and cohort designs, with

adjustment for age. Risk windows of 1-7 and 1-21

days were evaluated. Cases of intussusception

were observed in temporal association within 21

days following the first dose of RotaTeq, with a

clustering of cases in the first 7 days. Based on the

results, approximately 1 to 1.5 excess cases of

intussusception occur per 100,000 vaccinated US

infants within 21 days following the first dose of

RotaTeq. In the first year of life, the background

rate of intussusception hospitalizations in the US

has been estimated to be approximately 34 per

100,000 infants.

ןולעב ןולעב

ןכרצל ןכרצל תורמחהה

תושקובמה

קרפ

ןולעב טסקט

יחכונ טסקט

שדח תועפות ןהמ יאוולה לש תויורשפאה ?קטהטור הזיא

עדימ

בושח

ףסונ ךילע

תעדל

?

י/הנפ

אפורל

לש

ךדלי

וא רדחל

ןוימ

לש

תיב

םילוח םא ,דימ

רחאל

לכ

תחא תונמהמ

לש

ךדלי ,קטהטור לבוס

,םילושלש ,תואקהמ יבאכ

ןטב

םד ,םירומח האוצב

וא

יוניש

תיישעב םינימסת .םיכרצה

ולא םילולע

תויהל

םינמיס

היעבל תיניצר

תנכסמו

,םייח תארקנה

תולשפתה

יעמה

intussusception

רשא

תשחרתמ

רשאכ

קלח יעמהמ

םסחנ

וא

.תוועתמ תולשפתה

יעמה

הלוכי תורקל

םג

רשאכ

אל

ןתינ ןוסיח

םרוגהו

ךכל

ךרדב

ללכ וניא

.עודי ב"הראב

ולבקתה

םיחוויד

לע תולשפתה

יעמה

רשא

התרק םימי

םיתעלו

תועובש

רחאל לצא .ןוסיחה

קלח

םידליהמ שרדנ

חותינ ,זופשא

לש םייעמה

וא

היהש

ךרוצ

ןקוחב דחוימ

לופיטל

היעבב

תוומ .וז האצותכ

תולשפתהמ

יעמה הרק

םג

.ןכ י/רוצ

רשק

םע

אפורה

ךלש וא

י/הנפ

דימ

רדחל

ןוימ

םא שי

ךדליל

יא

וליא

םינימסתהמ לש

תולשפתה

םג ,יעמה

םא ופלח

רפסמ

תועובש

תנממ ןוסיחה

.הנורחאה י/הנפ

אפורל

לש

ךדלי

וא

רדחל

ןוימ

לש

תיב םילוח

םא ,דימ

ךדלי

לבוס

לכמ

תחא תויעבהמ

תואבה

רחאל

תלבק

םג ,קטהטור םא

ורבע

רפסמ

תועובש

זאמ

הנמה ןוויכ ,הנורחאה

ולאש

תולולע

תויהל

םינמיס היעבל

תארקנה ,תיניצר

תולשפתה

יעמה

intussusception

האקה

הרומח

לושלש

רומח

באכ

ןטב

רומח

םד

.האוצב תולשפתה

יעמה

תשחרתמ

רשאכ

קלח יעמהמ

םסחנ

וא

.תוועתמ זאמ

רושיא

ןוסיחה

ידי-לע

תויושר

תואירבה תוצראב

תירבה

ולבקתה ,

םיחוויד

לע תולשפתה

יעמה

תוקוניתב

רחאל

תלבק ידי-לע ,קטהטור

תכרעמ

חווידל

תועפות

יאוול םינוסיחב

VAERS

תולשפתה .

יעמה

התרק םימי

םיתעלו

תועובש

רחאל

לצא .ןוסיחה קלח

םידליהמ

שרדנ

חותינ ,זופשא

לש םייעמה

וא

היהש

ךרוצ

ןקוחב

דחוימ

לופיטל היעבב

תוומ .וז

האצותכ

תולשפתהמ

יעמה הרק

םג

.ןכ רקחמ

םייקתהש

רחאל

רושיא

קטהטור הארה

הילע

ירקמב

תולשפתה

יעמה

ךלהמב

םימיה

רחאלש

הנמה

הנושארה

לש ךא ,קטהטור

דחוימב

םימיה

םינושארה

:תוללוכ וחוודש תופסונ יאוול תועפות תורומח תויהל תולולע רשא ,תויגרלא תועפות םיישק ,הפהו םינפה לש תוחיפנ לולכלו םיפוצפצ ,המישנב

תיגרלא הבוגת) תלרח ,(רועב תירוע החירפ וא/ו

Page 2 of 3

םיעוריא

רשא

והוז

וא

וחווד

תועפותכ

יאוול רחאל

ןוסיח

קטהטורב

םילוכי

תורקל

םג רשאכ

אל

ןתינ

ןוסיח

Page 3 of 3

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