Sanofi Pasteur MSD Limited

In section 1: update according to standard terms

In section 2: editorial revision

In section 3: editorial revision

In section 4.1: update the age indication and editorial revision

In section 4.2: update the age indication and editorial revision

In section 4.3: The contraindications section has been reworded and completed

In section 4.4: The warnings and precautions information has been re-organized to follow the prescription/ administration steps and by order of importance. Information on history of febrile convulsions has been added. - Information on residuals moved to section 4.3.

In section 4.5: Concomitant administration of Pediacel with measles, mumps and rubella (MMR) and varicella vaccines has been added

In section 4.8: The section Undesirable Effects has been modified to reflect the data presented in the dossier for Pediacel Syringe in DCP approved on 05 December 2010. The data submitted with Pediacel Syringe in DCP give a more accurate safety picture of the product. Minor rewording and reformatting have been added.

In section 5.1: The section Pharmacological Properties has been modified to reflect the data presented in the dossier for Pediacel Syringe in DCP approved on 05 December 2010. The data submitted with Pediacel Syringe in DCP give more accurate pharmacological information of the product.

Section 4.1
addition of sentance - "in accordance with applicable official recommendations".
Section 4.5
Minor revision to text
Section 4.8
Reformatting and addition of side effects following PSUR assessment.

4.8       Undesirable Effects

Data from Clinical Trials

(...)

There was a trend for an increased frequency of injection site reactions when a fourth dose of PEDIACEL was given to 401 children in the second year of life. Pain was reported in 33%, erythema in 23% and oedema in 16% compared to rates of 18%, 11% and 11%, respectively, during the primary series. The frequency of systemic reactions was similar whether PEDIACEL was administered in infancy or in the second year of life.

In a controlled clinical study of PEDIACEL, administered concomitantly with meningococcal group C conjugate vaccine, 71% of 121 infants immunised at 2, 3 and 4 months experienced a reaction (pain, erythema or oedema) at the PEDIACEL injection site within the first seven days after vaccination. Also, 92% of infants experienced a systemic reaction within the first seven days after vaccination. The rates of moderate to severe reactions were similar to those described at 2, 4 and 6 months.

The following adverse events have been reported during clinical studies conducted with PEDIACEL and spontaneously reported during post-marketing use of PEDIACEL worldwide.

Adverse reactions are ranked under headings of frequency 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), including individual cases

Not Known            cannot be estimated from the available data

Data from Clinical Trials

The reactions observed were as follows:

Metabolism and Nutrition Disorders

Common (1-10%)              Appetite loss.

Psychiatric Disorders

Very Common                    Irritability.

Very rare (<0.01%)             Abnormal crying.

Nervous system disorders

Rare (0.01-0.1%):              Febrile convulsions.

Gastrointestinal disorders

Common(1-10%):              Diarrhoea and vomiting.

General disorders and administration site conditions

Very common(>10%):        Pain, erythema and oedema at the injection site.

                                           Irritability, dDecreased activity, increased crying and pyrexia (>38°C).

 
Very rare (<0.01%) Very rarely,           Large injection site reactions (>50 mm), and extensive limb swelling from the injection site beyond one or both joints., have been reported following administration of PEDIACEL. These reactions start within 24-72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve  spontaneously within 3-5 days. The risk appeared to be dependent on the number of prior doses of acellular pertussis containing vaccine, with a greater risk following the 4th and 5th doses.

In a controlled clinical study of PEDIACEL, administered concomitantly with meningococcal group C conjugate vaccine, 71% of 121 infants immunised at 2, 3 and 4 months experienced a reaction (pain, erythema or oedema) at the PEDIACEL injection site within the first seven days after vaccination. Also, 92% of infants experienced a systemic reaction within the first seven days after vaccination. The rates of moderate to severe reactions were similar to those described at 2, 4 and 6 months.

Data from Post-marketing Experience

Based on spontaneous reporting, the following adverse events have been reported following the commercial use of PEDIACEL. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Therefore, the frequency category “Not Known” is assigned to these adverse events.

Immune System Disorders

Hypersensitivity, anaphylactic reaction (such as urticaria, angioedema).

Nervous System Disorders

Afebrile convulsion, high-pitched crying, hypotonic hyporesponsive episode (infant appears pale, hypotonic (limp) and unresponsive) to parents, somnolence.

Vascular Disorders

Pallor

Psychiatric Disorders

Screaming.

Skin and Subcutaneous Tissue Disorders

Rash.

Musculoskeletal, Connective Tissue and Bone Disorders

Pain in vaccinated limb.

General Disorders and Administration Site Conditions

Pyrexia (>40.5°C), injection site mass, pallor, somnolence, asthenia, and listlessness.

Edematous reactions affecting one or both lower limbshave occurred following vaccination with H. influenzae type b containing vaccines. When this reaction occurs, it does so mainly after primary injections and is observed within the first few hours following vaccination. Associated symptoms may include cyanosis, redness, transient purpura and severe crying. All events resolved spontaneously without sequelae within 24 hours.

Description of Selected Adverse Reactions

General Disorders and Administration Site Conditions

Very rarely, large injection site reaction (>50 mm), and extensive limb swelling from the injection site beyond one or both joints, have been reported following administration of PEDIACEL. These reactions start within 24-72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3-5 days. The risk appeared to be dependent on the number of prior doses of acellular pertussis containing vaccine, with a greater risk following the 4^th and 5^th doses.

Edematous reactions affecting one or both lower limbs have occurred following vaccination with H. influenzae type b containing vaccines. When this reaction occurs, it does so mainly after primary injections and is observed within the first few hours following vaccination.

Associated symptoms may include cyanosis, redness, transient purpura and severe crying. All events resolved spontaneously without sequelae within 24 hours.

OtherAdditional Information on Special Populations

Apnoea in very premature infants (≤28 weeks of gestation). (See Section 4.4.)

Section 10
update the revision date to 20-04-2010

Change to section 4.4 – Special warnings & precautions for use Addition of warning on risk of apnoea in very premature infants following vaccination as per EMEA requirement for all vaccines that could be given to premature infants.

Change to section 4.8 – Undesirable effects Addition of Apnoea in very premature infants (≤ 28 weeks of gestation) as per EMEA requirement for all vaccines that could be given to premature infants.

Change to section 10 – Date of partial revision of the text Changed to June 2008 (variation approval date)

Section 2

Change fimbrial agglutinogens to fimbriae

Section 3

Addition of “PEDIACEL® is a sterile, uniform, cloudy, white to off-white suspension.”

Section 4.3

Addition of contra-indications for encephalopathy following previous Pertussis vaccines and progressive neurologic disorder, uncontrolled epilepsy, or progressive encephalopathy.

Section 4.4

Addition of warning statement regarding Guillain-Barré syndrome or brachial neuritis.

Section 4.8

Addition of extensive limb swelling, Oedematous reactions, Afebrile convulsions, Pallor and Somnolence

Section 9

Addition of licence renewal date: 15 October 2007

Section 10

Changed to December 2007