TRIPACELP®P is indicated for the primary immunization of infants from the age of 2 months and in children up to 6 years of age (prior to their 7th birthday) against diphtheria, tetanus and pertussis (whooping cough).
Children who have had diphtheria, tetanus or pertussis should still be immunized since these clinical infections do not always confer immunity.
Human Immunodeficiency Virus (HIV)-infected persons, both asymptomatic and symptomatic, should be immunized against diphtheria, tetanus and pertussis according to standard schedules.
TRIPACELP®P is not to be used for the treatment of disease caused by Corynebacterium diphtheriae, Clostridium tetani or Bordetella pertussis infections.
30BPediatrics
TRIPACELP®P is not indicated for persons less than 2 months of age or persons 7 years of age or older.
31BGeriatrics
TRIPACELP®P is not indicated for use in adult and elderly populations.

For routine immunization, TRIPACELP®P is recommended as a 4-dose series, with a single dose of 0.5 mL of TRIPACELP®P at 2, 4, 6 and 18 months of age.
If for any reason this schedule is delayed, it is recommended that 3 doses be administered with an interval of 2 months between each dose, followed by a fourth dose approximately 6 to 12 months after the third dose.
Whenever feasible, TRIPACELP®P should be used for all 4 doses in the vaccination series as there are no clinical data to support the use of TRIPACELP®P with any other licensed acellular pertussis combination vaccine in a mixed sequence.
Premature infants whose clinical condition is satisfactory should be immunized with full doses of vaccine at the same chronological age and according to the same schedule as full-term infants, regardless of birth weight. Fractional doses (doses <0.5 mL) should not be given. The effect of fractional doses on the safety and efficacy has not been determined.
The childhood immunization series may be completed with a single 0.5 mL dose of DTaP such as TRIPACELP®P between 4 and 6 years of age.
TRIPACELP®P should not be administered to persons less than 2 months or to persons 7 years of age or older.

32BMethod of Administration
Before injection, the skin over the site to be injected should be cleansed with a suitable germicide. Administer the total volume of 0.5 mL intramuscularly (I.M.). In infants younger than 1 year, the anterolateral aspect of the thigh provides the largest muscle and is the preferred site of injection. In older children the deltoid muscle is usually large enough for injection.
For instructions for preparation of the medicinal product before administration, see section 6.6.

Hypersensitivity Known systemic hypersensitivity reaction or a life threatening reaction to any component of TRIPACELP®P after previous administration of the vaccine or a vaccine containing one or more of the same components are contraindications to vaccination. Because of uncertainty as to which component of the vaccine may be responsible, none of the components should be administered. Alternatively, such persons may be referred to an allergist for evaluation if further immunizations are considered. Neurological Disorders The following events are contraindications to administration of any pertussis-containing vaccine, including TRIPACELP®P: Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause. Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, progressive encephalopathy. Pertussis vaccine should not be administered to persons with such conditions until a treatment regimen has been established and the condition has stabilized.

General
Before administration of TRIPACELP®P health-care providers should inform the parent or guardian of the recipient to be immunized of the benefits and risks of immunization, inquire about the recent health status of the recipient, review the recipient’s history concerning possible hypersensitivity to the vaccine or similar vaccine, previous immunization history, the presence of any contraindication to immunization and comply with any local requirements with respect to information to be provided to the parent or guardian before immunization and the importance of completing the immunization series.
It is extremely important that the parent or guardian be questioned concerning any symptoms and/or signs of an adverse reaction after a previous dose of vaccine.
The rates and severity of adverse events in recipients of tetanus toxoid are influenced by the number of prior doses and level of pre-existing antitoxins.

Syncope (fainting) has been reported following vaccination with TRIPACEL®. Procedures should be in place to prevent falling injury and manage syncopal reactions.
As with any vaccine, TRIPACELP®P may not protect 100% of vaccinated individuals.
Administration Route Related Precautions: Do not administer TRIPACELP®P by intravascular injection: ensure that the needle does not penetrate a blood vessel.
Intradermal or subcutaneous routes of administration are not to be utilized.
TRIPACELP®P should not be administered into the buttocks.
Febrile and Acute Disease: Vaccination should be postponed in cases of an acute or febrile disease. However, a disease with low-grade fever should not usually be a reason to postpone vaccination.
If any of the following events occur within the specified period after administration of a whole-cell pertussis vaccine or a vaccine containing an acellular pertussis component, the decision to administer TRIPACELP®P should be based on careful consideration of potential benefits and possible risks.
• Temperature of ≥40.5°C (105°F) within 48 hours, not attributable to another identifiable cause;
• Collapse or shock-like state (hypotonic-hyporesponsive episode - HHE) within 48 hours;
• Persistent crying lasting ≥3 hours within 48 hours;
• Convulsions with or without fever within 3 days.
Hematologic
Because any intramuscular injection can cause an injection site hematoma in persons with any bleeding disorders, such as hemophilia or thrombocytopenia, or in persons on anticoagulant therapy, intramuscular injections with TRIPACELP®P should not be administered to such persons unless the potential benefits outweigh the risk of administration. If the decision is made to administer any product by intramuscular injection to such persons, it should be given with caution, with steps taken to avoid the risk of hematoma formation following injection.
Immune
The possibility of allergic reactions in persons sensitive to components of the vaccine should be evaluated. Hypersensitivity reactions may occur following the use of TRIPACELP®P even in persons with no prior history of hypersensitivity to the product components. Cases of allergic or anaphylactic reactions have been reported after receiving some preparations containing diphtheria and tetanus toxoids and/or pertussis antigens.
Epinephrine hydrochloride solution (1:1,000) and other appropriate agents should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs (see section 4.8). Health-care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management.
Immunocompromised persons (whether from disease or treatment) may not obtain the expected immune response. If possible, consideration should be given to delaying vaccination until after the completion of any immunosuppressive treatment. Nevertheless, vaccination of persons with chronic immunodeficiency such as HIV infection is recommended even if the immune response might be limited.
Neurologic
A review by the US Institute of Medicine (IOM) found evidence for a causal relationship between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome (GBS). ACIP recommends that if GBS occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give TRIPACELP®P or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.
For infants or children at higher risk for seizures than the general population that an appropriate antipyretic may be administered (in the dosage recommended in its prescribing information) at the time of vaccination with a vaccine containing an acellular pertussis component (including TRIPACELP®P) and for the following 24 hours, to reduce the possibility of post-vaccination fever.
Hypotonic-hyporesponsive episodes (HHEs) rarely follow vaccination with whole-cell pertussis-containing DTP vaccines and occur even less commonly after acellular pertussis-containing DTP and DT vaccines. A history of HHE is not a contraindication to the use of acellular pertussis vaccines, but recommends precaution in these cases.
Pregnant Women
The vaccine should not be administered to pregnant women.
Nursing Women
The vaccine should not be administered to nursing women.
Pediatrics
The potential risk of apnea and the need for respiratory monitoring for 48 – 72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

33BVaccine-Drug Interactions
Immunosuppressive treatments may interfere with the development of the expected immune response. (see section 4.4)
34BConcomitant Vaccine Administration
Administering the most widely used live and inactivated vaccines during the same patient visit has produced seroconversion rates and rates of adverse reactions similar to those observed when the vaccines are administered separately.
Vaccines administered simultaneously should be given using separate syringes at separate sites. Simultaneous administration is suggested, particularly when there is concern that a person may not return for subsequent vaccination. Simultaneous administration of childhood vaccines such as TRIPACELP®P, MMR, varicella, pneumococcal conjugate and hepatitis B vaccines, is encouraged for children who are at the recommended age to receive these vaccines and for whom no contraindications exist.
TRIPACELP®P may be used to reconstitute Act-HIBP®P [Haemophilus b Conjugate Vaccine (Tetanus Protein-Conjugate)] permitting the administration of these vaccines in a single dose.

Not applicable. TripacelP® Pis not intended for administration to women of child-bearing age.

Not relevant. TripacelP® Pis not indicated for persons 7 years of age and older.4.8

Clinical Trial Adverse Reactions
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 rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events.
TRIPACELP®P has been safely administered to over 4,000 children in clinical trials. In these trials, recipients of TRIPACELP®P consistently experienced lower rates of injection site and systemic solicited reactions than those receiving whole-cell pertussis vaccines. The size and frequency of injection site reactions increase with the number of doses administered. Although these injection site reactions may produce large injection site swelling, pain is generally limited.
In a clinical study conducted in Canada, 324 children received TRIPACELP®P at 2, 4, 6 and 18 months of age. In another Canadian study, 21 children received TRIPACELP®P at 4-6 years of age. The following rates of reactions were observed:

In a clinical trial in Sweden comparing 2 acellular pertussis vaccines, DT and a whole-cell DTP vaccine, 2,587 infants received TRIPACELP®P at 2, 4 and 6 months of age. Rates of adverse events following TRIPACELP®P administration were similar to those following DT and significantly lower than following whole-cell DTP. There were 2 reports of fever >40°C and 1 report of an HHE following TRIPACELP®P administration. There were 7 reports of convulsions, but none were within 7 days of vaccination.
In another clinical trial conducted in Sweden comparing 3 acellular pertussis vaccines and 1 whole-cell DTP vaccine, 20,745 infants received a different formulation (20 μg PT, 20 μg FHA, 3 μg PRN, 5 μg FIM) of TRIPACELP®P at 2, 4 and 6 or 2, 5 and 12 months of age. Rates of adverse events were less than or comparable to the rates in the other acellular pertussis vaccine and whole-cell DTP groups in this study. The rates of reports of fever >40.5°C and seizures or suspected seizures were significantly higher following whole-cell DTP than following acellular pertussis vaccines. Rates of HHE were comparable, with 29 reports following administration of TRIPACELP®P. No deaths or cases of encephalitis or acute encephalopathy, invasive bacterial infection, infantile spasms or anaphylactic reactions were reported within 48 hours of vaccination.
Data from Post-Marketing Experience
The following additional adverse events have been spontaneously reported during the post-marketing use of TRIPACELP®P worldwide. 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. Decisions to include these events in labelling were based on one or more of the following factors: 1) severity of the event, 2) frequency of reporting or 3) strength of causal connection to TRIPACELP®P.
Blood and Lymphatic Disorders
Lymphadenopathy
Cardiac Disorders
Cyanosis
Gastro-intestinal Disorders
Nausea, diarrhea

General Disorders and Administration Site Conditions
Injection site reactions: pain, rash, nodule, mass
Large injection site reactions (>50 mm), including extensive limb swelling which may extend from the injection site beyond one or both joints have been reported in children following TRIPACELP®P administration. These reactions usually 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 appears to be dependent on the number of prior doses of acellular pertussis containing vaccine, with a greater risk following the 4PthP and 5PthP doses.
Infections and Infestations
Injection site cellulitis, cellulitis, injection site abscess
Immune System Disorders
Hypersensitivity, allergic reaction, anaphylactic reaction (edema, face edema)
Pruritus, generalized rash and other types of rash (erythematous, macular, maculo-papular)
Nervous System Disorders
Convulsions: febrile convulsion, grand mal convulsion, partial seizures
Hypotonic-hyporesponsive episode, hypotonia, somnolence and Syncope (fainting).
Psychiatric Disorders
Screaming
To report any side effect(s):
•Saudi Arabia:
- National Pharmacovigilance Center (NPC):
o Fax: +966-11-205-7662
o Call NPC at :
+966-11-2038222 Exts: 2317-2356-2353-2354-2334-2340
o Toll free: 8002490000
o E-mail: Unpc.drug@sfda.gov.saU
o Website: www.sfda.gov.sa/npc

Not applicable.

Pharmacotherapeutic group: Vaccine against diphtheria, tetanus and pertussis.
ATC Code J07AJ52
Mechanism of Action
Diphtheria and Tetanus: Strains of C. diphtheriae that produce diphtheria toxin can cause severe or fatal illness characterized by membranous inflammation of the upper respiratory tract and toxin-induced damage to the myocardium and nervous system. Protection against disease attributable to C. diphtheriae is due to the development of neutralizing antibodies to diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is considered the lowest level giving some degree of protection. Antitoxin levels of at least 0.1 IU/mL are generally regarded as protective Levels of 1.0 IU/mL have been associated with long-term protection.
Tetanus is an acute and often-fatal disease caused by an extremely potent neurotoxin produced by C. tetani. The toxin causes neuromuscular dysfunction, with rigidity and spasms of skeletal muscles. Protection against disease attributable to C. tetani is due to the development of neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assay, is considered the minimum protective level. Levels of 1.0 IU/mL have been associated with long-term protection.
In a clinical trial in Canada (N = 324), protective levels of diphtheria and tetanus antitoxin antibodies were present in all but one participant after 3 doses of TRIPACELP®P and in 100% after four doses.
Pertussis: Pertussis (whooping cough) is a respiratory disease caused by B. pertussis. This Gram-negative coccobacillus produces a variety of biologically active components, though their role in either the pathogenesis of, or immunity to, pertussis has not been clearly defined. The mechanism of protection from B. pertussis disease is not well understood. However, in a clinical trial in Sweden (Sweden I Efficacy Trial), the same pertussis components as in TRIPACELP®P (i.e., PT, FHA, PRN and FIM) have been shown to prevent pertussis in infants with a protective efficacy of 85.2% using the World Health Organization (WHO) case definition (≥21 consecutive days of paroxysmal cough with culture or serologic confirmation or epidemiological link to a confirmed case). In the same study, the protective efficacy against mild disease was 77.9%.
Minimum serum antibody levels to specific pertussis vaccine components that confer protection against the development of clinical pertussis have not been identified. Nevertheless, a number of studies have demonstrated a correlation between the presence of serum antibody responses to pertussis vaccine components and protection against clinical disease. In a controlled clinical trial in Sweden (Sweden II Trial), the efficacy of a DTaP vaccine with a different formulation in pertussis antigens as TRIPACELP®P was demonstrated to provide a two-fold to three-fold higher protection against pertussis with any cough compared to the three pertussis antigens vaccine. The observed difference supports the role of fimbriae types 2 and 3 in the protection against colonization of B. pertussis and mild disease.
Duration of Effect
To ensure optimal protection during childhood, 4 consecutive doses should be given at 2, 4, 6 and 18 months of age. A booster with a vaccine containing diphtheria, tetanus, acellular pertussis with or without IPV is required at 4 to 6 years.

No pharmacokinetic studies have been performed.

Data from animal studies revealed no unexpected findings and no target organ toxicity.

Aluminum Phosphate (adjuvant) (aluminum 0.33 mg) 1.5 mg
2-phenoxyethanol

This vaccine must not be mixed with other medicinal products except Act-HIBP®P [Haemophilus b Conjugate Vaccine (Tetanus Protein-Conjugate)] as mentioned in section 4.5.

3 years.

Store at 2° to 8°C (35° to 46°F). Do not freeze. Discard product if exposed to freezing.

Do not use after expiration date.

TRIPACELP®P is supplied in single dose vials.
The vials are made of Type 1 glass. The vial stopper for this product does not contain latex (natural rubber).
TRIPACELP®P is available in a package of
1 x 0.5 mL (single dose) vial

Inspect for extraneous particulate matter and/or discolouration before use. If these conditions exist, the product should not be administered.
Shake the vial well until a uniform, cloudy, suspension results. Cleanse the vial stopper with a suitable germicide prior to withdrawing the dose. Do not remove either the stopper or the metal seal holding it in place.
Aseptic technique must be used. Use a separate sterile syringe and needle or a sterile disposable unit, for each individual patient to prevent disease transmission. Needles should not be recapped but should be disposed of according to biohazard waste guidelines