Infanrix-IPV, suspension for injection in pre-filled syringe.

Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed).

One dose (0.5 ml) contains:

¹adsorbed on aluminium hydroxide,hydrated 0.5 milligrams Al³⁺

²propagated in VERO cells

For a full list of excipients, see section 6.1.

Suspension for injection in pre-filled syringe.

Infanrix-IPV is a turbid white suspension.

This vaccine is indicated for booster vaccination against diphtheria, tetanus, pertussis, and poliomyelitis diseases in individuals from 16 months to 13 years of age inclusive.

The administration of Infanrix-IPV should be based on official recommendations.

Posology

A single dose of 0.5 ml should be administered.

Infanrix-IPV may be administered to subjects who have previously received whole cell or acellular pertussis-containing vaccines, and oral live attenuated or injected inactivated poliomyelitis vaccines. (See also sections 4.8 and 5.1).

Method of administration

The vaccine is for intramuscular injection, usually into the deltoid muscle. However, the anterolateral thigh may be used in very young subjects if preferred.

Do not administer intravascularly.

Hypersensitivity to the active substances or to any of the excipients or neomycin, polymyxin or formaldehyde.

Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, or polio vaccines.

Infanrix-IPV should not be administered to subjects who experienced neurological complications (for convulsions or hypotonic-hyporesponsive episodes, see section 4.4) following previous immunisation with any of the antigens in the vaccine.

Infanrix-IPV should not be administered to subjects who experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with a pertussis containing vaccine.

As with other vaccines, administration of Infanrix-IPV should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection is not a contra-indication.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination. A family history of convulsions or a family history of Sudden Infant Death Syndrome (SIDS) does not constitute a contra-indication.

If any of the following events are known to have occurred in temporal relation to receipt of pertussis-containing vaccine, the decision to give further doses of pertussis-containing vaccines should be carefully considered:

- temperature of 40.0°C within 48 hours, not due to another identifiable cause,

- collapse or shock-like state (hypotonic-hyporesponsiveness episode) within 48 hours of vaccination,

- persistent, inconsolable crying lasting 3 hours, occurring within 48 hours of vaccination,

- convulsions with or without fever, occurring within 3 days of vaccination.

There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks.

Infanrix-IPV should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.

HIV infection is not considered as a contra-indication. The expected immunological response may not be obtained after vaccination of immunosuppressed patients.

For children under immunosuppressive treatment (corticosteroid therapy, antimitotic chemotherapy, etc.), it is recommended to postpone vaccination until the end of treatment.

Infanrix-IPV should under no circumstances be administered intravascularly.

Infanrix-IPV has been administered concomitantly with measles-mumps-rubella vaccine or Hib vaccine in clinical trials. The data available do not suggest any clinically relevant interference in the antibody response to each of the individual antigens.

Interaction studies have not been carried out with other vaccines, biological products or therapeutic medications. However, in accordance with commonly accepted immunisation guidelines, since Infanrix-IPV is an inactivated product, there is no theoretical reason why it should not be administered concomitantly with other vaccines or immunoglobulins at separate sites.

As with other vaccines it may be expected that in patients receiving immunosuppressive therapy or patients with immunodeficiency, a protective immune response to one or more antigens in the vaccine may not be achieved.

It is anticipated that Infanrix-IPV would only rarely be administered to subjects of child-bearing potential. Adequate human data on the use of Infanrix-IPV during pregnancy and lactation are not available and animal studies on reproductive toxicity have not been conducted. Consequently the use of this combined vaccine is not recommended during pregnancy. It is preferable to avoid the use of this vaccine during lactation.

It is anticipated that Infanrix-IPV would only rarely be administered to subjects who would be driving or using machines. However, somnolence, commonly reported after vaccination, may temporarily affect the ability to drive and use machines.

Clincical Trials: The safety of Infanrix-IPV has been evaluated in 2030 subjects in clinical studies. All vaccinees had previously received either 3 or 4 doses of a combined diphtheria, tetanus and pertussis vaccine. These vaccines contained either whole cell (Pw) or acellular (Pa) pertussis components as follows:

-736 children aged 15-26 months had previously been given 3 doses of DTP –37 had received DTPw, 699 had received DTPa,

– 593 children aged 4-7 years had previously been given either 3 or 4 doses of DTP – 128 had received 3 doses of DTPw, 211 had received 3 doses of DTPa, 73 had received 4 doses of DTPw, 181 had received 4 doses of DTPa

– 701 children aged 10-14 years had received 4 doses of DTPw

All had received a full primary course of either IPV or OPV. Vaccinees aged 10-14 years had also received an additional dose of diphtheria, tetanus and polio antigens at approximately 5-6 years.

Booster doses of DTPa-containing vaccines may be more reactogenic in children who have been previously primed with acellular pertussis-containing vaccines.

Adverse reactions reported during these studies were mostly reported within 48 hours following vaccination, were of mild to moderate severity and resolved spontaneously.

Frequencies are defined as follows:

Very common: 10%

Common: 1% and < 10%

Uncommon: 0.1% and < 1%

Rare: 0.01% and < 0.1%

Not known: cannot be estimated from the available data

Infections and infestations

Rare: pharyngitis

Blood and lymphatic system disorders

Uncommon: lymphadenopathy

Metabolism and nutrition disorders

Very common: loss of appetite

Psychiatric disorders:

Very common: irritability, restlessness, unusual crying

Uncommon: insomnia

Nervous system disorders:

Very common: headache, somnolence

Eye disorders

Rare: eye pain

Ear and labyrinth disorders

Rare: earache

Respiratory, thoracic and mediastinal disorders

Uncommon: rhinitis, coughing

Gastrointestinal disorders:

Common: nausea, vomiting, diarrhoea

Uncommon: abdominal pain

Skin and subcutaneous tissue disorders

Uncommon: rash

Rare: pruritis

Musculoskeletal and connective tissue disorders

Uncommon: back pain

Renal and urinary disorders

Uncommon: urinary incontinence

General disorders and administration site conditions:

Very common: pain, redness and swelling at the injection site*, fever, malaise

Common: asthenia

* Information on extensive swelling of the injected limb (defined as swelling with a diameter> 50 mm, noticeable diffuse swelling or noticeable increase of limb circumference) occurring after Infanrix-IPV was actively solicited in two clinical trials. When Infanrix-IPV was administered as either a fourth dose or a fifth dose of DTPa to children 4-6 years of age, extensive injection site swelling was reported with incidences of 13% and 25% respectively. The most frequent reactions were large, localised swelling (diameter> 50 mm) occurring around the injection site. A smaller percentage of children (3% and 6% respectively) experiences diffuse swelling of the injected limb, sometimes involving adjacent joint. In general, these reactions began within 48 hours of vaccination and spontaneously resolved over an average of 4 days without sequelae.

Post marketing surveillance: Not known: For the following adverse events identified during post-marketing surveillance, an exact quantification of frequency cannot be established.

Immune system disorders

Allergic reactions, including anaphylactoid reactions

Nervous system disorders:

Convulsions, collapse or shock-like state (hypotonic-hyporesponsiveness episode)

Skin and subcutaneous tissue disorders

Urticaria

No case of overdose has been reported.

Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code: J07CA02

The immune response after booster vaccination with Infanrix-IPV was evaluated in 917 vaccinees. The immune response observed was independent of the number of doses and type of vaccines administered previously (DTPw or DTPa, OPV or IPV) as shown in the tables below.

One month after vaccination of children aged 15 to 26 months, the immune responses were the following:

* These levels are considered to be protective

One month after vaccination of children aged 4-7 years, the immune responses were the following:

* These levels are considered to be protective

One month after vaccination of children/adolescents aged 10-13 years, the immune responses were the following:

* These levels are considered to be protective

After vaccination, 99% of all subjects had protective antibody levels against diphtheria, tetanus and the three poliovirus types.

No serological correlate of protection has been defined for the pertussis antigens. The antibody titres to the three pertussis components were in all cases higher than those observed after primary vaccination with the paediatric acellular pertussis combination vaccine (DTPa, Infanrix™), for which efficacy has been demonstrated in a household contact efficacy study. Based on these comparisons, it can therefore be anticipated that Infanrix-IPV would provide protection against pertussis, although the degree and duration of protection afforded by the vaccine are undetermined.

Evaluation of pharmacokinetic properties is not required for vaccines.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety, specific toxicity and compatibility of ingredients.

Sodium chloride

Medium 199 (containing principally amino acids, mineral salts, vitamins)

Water for injections

For adjuvants, see section 2.

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

3 years.

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Store in the original package, in order to protect from light.

0.5 ml of suspension for injection in a pre-filled syringe (type I glass) with plunger stopper (butyl) - pack sizes of 1 or 20.

Upon storage, a white deposit and clear supernatant may be observed. This does not constitute a sign of deterioration.

The syringe should be well shaken in order to obtain a homogeneous turbid white suspension.

The suspension should be inspected visually for any foreign particulate matter and/or abnormal physical appearance. In the event of either being observed, discard the vaccine.

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

SmithKline Beecham plc

Trading as:

GlaxoSmithKline UK

Stockley Park West, Uxbridge

Middlesex UB11 1BT

PL10592/0209

7 August 2006

29 October 2008

POM