Test Summaries
In this article
Summary
Key points
- Both hexavalent vaccines demonstrate an overall favorable and clinically acceptable safety profile for routine primary immunization
- DT3aP-based hexavalent vaccine is associated with a statistically significant reduction in injection-site reactions (pain, erythema, swelling) compared to DT2aP
- Vomiting rates are comparable between DT3aP and DT2aP formulations, suggesting no additional systemic safety trade-off
Introduction
Hexavalent vaccines containing antigens against diphtheria, tetanus, pertussis, Haemophilus influenzae type b, poliomyelitis, and hepatitis B are used in India for the primary immunization schedule at 6, 10, and 14 weeks, as well as for the toddler booster dose.1
Combination vaccines protect against multiple diseases while reducing the number of injections administered during the first two years of life, thereby simplifying vaccination schedules. The Advisory Committee on Immunization Practices (ACIP) recommends the use of combination vaccines over lower-valent vaccines when licensed and indicated, provided they are not less immunogenic, less effective, or more reactogenic. Combination vaccines offer greater economic value when the direct and indirect costs associated with additional injections, delayed or missed vaccinations, and increased storage and handling requirements are considered.1
Infants born prematurely (<37 weeks of gestation) or with low birth weight (<2500 g) are at increased risk of infections due to immature physical and immunological defense mechanisms.2 Despite recommendations that preterm and low-birth-weight infants follow the same chronological immunization schedule as full-term infants, vaccination is often delayed due to concerns about safety and immune responsiveness in this vulnerable population.2
Understanding the safety and immunogenicity of hexavalent vaccines in preterm infants is therefore critical for ensuring timely protection.1,2
Evidence Base for Hexavalent Vaccination in Preterm Infants2
Available evidence comes from several clinical studies and post-marketing safety surveillance evaluating the hexavalent diphtheria–tetanus–acellular pertussis–hepatitis B–inactivated poliovirus–Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine in infants with a history of prematurity. Overall, 10 clinical studies have assessed this vaccine in preterm or low-birth-weight infants, including studies where it was administered alone or alongside other pediatric vaccines such as pneumococcal conjugate vaccines and rotavirus vaccines.2
Study population2
1600 preterm infants received the hexavalent vaccine across studies.
- 596 infants born at ≤32 weeks gestation
- 127 infants born at <29 weeks gestation
Safety Outcomes
Common adverse reactions2
Occurrence and intensity of solicited local and general symptoms were similar in preterm and full-term infants.
Commonly reported events:
- Fever
- Drowsiness
- Irritability
- Injection-site reactions
These events were not influenced by birth weight or gestational age.
Cardiorespiratory Events
The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention.1,2
Event |
Observation |
Apnea/bradycardia in vaccinated infants |
59.1% (95% CI 48.5-69.2) |
Apnea/bradycardia in non-vaccinated controls |
58.2% (95% CI 47.8-68.1) |
Statistical difference |
None observe |
Adapted from Omeñaca F, et al. Vaccine. 2018
Additionally, among the vaccinated group there were no differences in the incidence or severity of events that occurred in the period before versus after vaccination. 2
Immunogenicity Results2
Seroprotection after primary vaccination
High seroprotection rates were observed after completion of the 3-dose primary series.2
Antibody |
Seroprotection / Vaccine Response (%) (95% CI) |
GMT (95% CI) |
Anti-HBs (≥10 mIU/ml) |
93.4 (86.2–97.2) |
634.1 (433.8–927.9) |
Anti-PRP (≥0.15 µg/ml) |
92.5 (85.1–96.9) |
2.2 (1.7–3.0) |
Anti-PRP (≥1.0 µg/ml) |
76.3 (66.4–84.5) |
— |
Anti-diphtheria (≥0.1 IU/ml) |
100 (96.1–100) |
3.7 (3.1–4.4) |
Anti-tetanus (≥0.1 IU/ml) |
100 (96.1–100) |
2.5 (2.1–2.9) |
Anti-poliovirus type 1 (≥1:8) |
100 (94.8–100) |
424.1 (308.7–582.7) |
Anti-poliovirus type 2 (≥1:8) |
100 (94.6–100) |
451.9 (319.8–633.6) |
Anti-poliovirus type 3 (≥1:8) |
100 (94.5–100) |
468.2 (312.0–702.8) |
Anti-PT vaccine response |
98.9 (94.2–100) |
61.3 (53.1–70.8) |
Anti-FHA vaccine response |
100 (96.1–100) |
239.5 (205.8–278.6) |
Anti-PRN vaccine response |
100 (96.1–100) |
155.3 (131.3–183.7) |
Adapted from Omeñaca F, et al. Vaccine. 2018
These findings demonstrate that most preterm infants develop protective antibody levels after primary immunization.
Booster response (18–20 months)
Booster vaccination resulted in substantial increases in antibody titers, indicating strong immune memory.2
Antibody |
Seroprotection / Vaccine Response (%) (95% CI) |
GMT (95% CI) |
Anti-HBs (≥10 mIU/ml) |
91.6 (83.4–96.5) |
1771.0 (1060.3–2958.1) |
Anti-PRP (≥0.15 µg/ml) |
100 (95.7–100) |
70.9 (56.0–89.8) |
Anti-PRP (≥1.0 µg/ml) |
100 (95.7–100) |
– |
Anti-diphtheria (≥0.1 IU/ml) |
100 (95.7–100) |
13.5 (11.5–15.9) |
Anti-tetanus (≥0.1 IU/ml) |
100 (95.7–100) |
7.8 (6.6–9.3) |
Anti-poliovirus type 1 (≥1:8) |
100 (95.5–100) |
1238.4 (1006.5–1523.8) |
Anti-poliovirus type 2 (≥1:8) |
100 (95.5–100) |
1471.9 (1201.9–1802.0) |
Anti-poliovirus type 3 (≥1:8) |
100 (95.1–100) |
1568.7 (1225.3–2008.3) |
Anti-PT vaccine response |
– |
58.9 (49.8–69.7) |
Anti-FHA vaccine response |
– |
578.4 (491.0–681.5) |
Anti-PRN vaccine response |
– |
456.3 (360.4–578.3) |
Adapted from Omeñaca F, et al. Vaccine. 2018
Following the primary vaccination series with the hexavalent vaccine, high seroprotection rates were observed across all antigens in preterm infants. Seroprotection reached 93.4% for hepatitis B, 92.5% for Hib (≥0.15 µg/ml), and 100% for diphtheria and tetanus, while 76.3% achieved the higher Hib threshold (≥1.0 µg/ml). Neutralizing antibodies against poliovirus were detected in 100% of infants for types 2 and 3, and in all evaluated participants for type 1. Strong responses were also observed for pertussis antigens. Following the 18–20-month booster, seroprotection reached 100% for diphtheria, tetanus, Hib, and all poliovirus serotypes, with markedly increased antibody titers, demonstrating strong immune memory and sustained immunogenicity in preterm infants.
Conclusion2
Available clinical evidence indicates that hexavalent DTPa-HBV-IPV/Hib vaccination in preterm infants demonstrates a favorable safety and immunogenicity profile. Adverse events were comparable to those observed in full-term infants, and cardiorespiratory events were largely associated with underlying prematurity rather than vaccination. High seroprotection rates were achieved after the primary series, with marked increases in antibody titers following the booster dose. Overall, these findings support timely immunization and indicate that hexavalent vaccination in preterm infants is as safe and effective in eliciting protective immune responses as in full-term infants.
CI: Confidence Interval; GMT: Geometric Mean Titer; HBs: Hepatitis B surface antigen; PRP: Poly Ribosylribitol phosphate (Haemophilus influenzae type b capsular polysaccharide); PT: Pertussis Toxin; FHA: Filamentous haemagglutinin; PRN: Pertactin; IU: International Units; mIU: Milli–International Units; µg: Micrograms
Key Safety Information3
Contraindications
Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.
Special warnings and precautions
Carefully consider decision to give further doses if: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Administer with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13.
Special populations
HIV infection not a contraindication. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity.
Pregnancy and Lactation
INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.
Undesirable effects
Very Common- Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ³38°C, local swelling at the injection site (≤50 mm), pain, redness.
For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory
References
- Chitkara AJ, Parikh R, Mihalyi A, Kolhapure S. Hexavalent Vaccines in India: Current Status. Indian Pediatr. 2019;56(11):939-950.
- Omeñaca F, Vázquez L, Garcia-Corbeira P, Mesaros N, Hanssens L, Dolhain J, Gómez IP, Liese J, Knuf M. Immunization of preterm infants with GSK’s hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: a review of safety and immunogenicity. Vaccine. 2018;36(7):986-996. doi:10.1016/j.vaccine.2018.01.005.
- Infanrix Hexa, Abbreviated Prescribing Information, Version: IFX-H/API/IN updated on 10 May 2023. https://india-pharma.gsk.com/media/a3hbdio3/infanrixhexa.pdf
GSK is not responsible for the third-party website content
For Healthcare Professionals Only
Key Safety Information
Contraindications
Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.
Special warnings and precautions
Carefully consider decision to give further doses if: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Administer with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13.
Special populations
HIV infection not a contraindication. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity.
Pregnancy and Lactation
INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.
Undesirable effects
Very Common- Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness
For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory
Abbreviated Prescribing information of INFANRIX HEXA [Diphtheria, tetanus, pertussis (acellular component), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed) Ph. Eur.]
ACTIVE INGREDIENT: Each 0.5 ml dose of reconstituted vaccine contains (i) Diphtheria toxoid ≥ 30 IU, (ii) Tetanus toxoid ≥ 40 IU, (iii) Bordetella pertussis antigens (Pertussis toxoid 25mcg, Filamentous Haemagglutinin 25 mcg, Pertactin 8 mcg), (iv) Hepatitis B surface antigen 10 mcg, (v) Inactivated Poliovirus [type 1 (Mahoney strain) 40 D-antigen unit, type 2 (MEF-1 strain) 8 D-antigen unit, type 3 (Saukett strain) 32 D-antigen unit), (vi) Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate, PRP) 10 mcg conjugated to tetanus toxoid as carrier protein (approximately 25 mcg).
INDICATION: Primary and booster vaccination of infants against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b.
DOSAGE AND ADMINISTRATION: Posology: The primary vaccination schedule should be administered according to official recommendations. Full-term infants or Preterm infants (≥24 weeks gestational age): 3-dose primary vaccination: interval of ≥1 month between primary doses. Booster dose ≥6 months after last priming dose; preferably ≤18 months of age. 2-dose primary vaccination: interval of ≥2 month between primary doses. Booster dose ≥6 months after last priming dose; preferably between 11-13 months of age. Administered according to official recommendations. The Expanded Program on Immunisation schedule (at 6, 10, 14 weeks of age) may only be used if hepatitis B vaccine given at birth. Safety and efficacy not been established in children > 36 months of age. Method of Administration: Deep intramuscular injection, preferably at alternating sites for subsequent injections.
CONTRA-INDICATIONS: Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.
SPECIAL WARNINGS and SPECIAL PRECAUTIONS: Precede vaccination by review of medical history and clinical examination. Protective immune response may not be elicited in all vaccinees. Will not prevent disease caused by pathogens other than Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus or Haemophilus influenzae type b. However, Hepatitis D can be expected to be prevent. If any following events have occurred in temporal relation to receipt of pertussis-containing vaccine, carefully considered decision to give further doses of pertussis-containing vaccines: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Appropriate medical treatment and supervision be available in case of rare anaphylactic event. Carefully weigh risk-benefit of immunising or deferring vaccination in infant or child suffering from new onset or progression of severe neurological disorder. Administered with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. History of febrile convulsions, family history of convulsions or Sudden Infant Death Syndrome (SIDS) not a contraindication for use. Vaccinees with history of febrile convulsions should be closely followed up. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13. Antipyretic treatment should be initiated according to local treatment guidelines. Special populations: HIV infection not a contraindication. Expected immunological response may not be obtained in immunosuppressed patients. Can be given to preterm infants; however lower immune response been observed for some antigens. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity. Benefit of vaccination is high; vaccination should not be withheld or delayed. Interference with laboratory testing: Hib capsular polysaccharide antigen excreted in urine, positive urine test observed within 1-2 weeks. Interaction with other medicinal products and other forms of interaction: INFANRIX HEXA can be given concomitantly with pneumococcal conjugate vaccine (PCV7, PCV10 and PCV13), meningococcal serogroup C conjugate vaccine (CRM197 and TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), oral rotavirus vaccine and measles-mumps-rubella-varicella (MMRV) vaccine. Pregnancy and Lactation: INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.
ADVERSE EFFECTS: The following drug-related adverse reactions were reported in clinical studies (data from more than 16,000 subjects) and during post-marketing surveillance.
Very common (≥1/10): Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness.
Common (≥1/100 to <1/10): Nervousness, diarrhoea, vomiting, fever >39.5°C, injection site reactions, including induration, local swelling at the injection site (>50 mm).
Uncommon (≥1/1,000 to <1/100): Upper respiratory tract infection, cough, diffuse swelling of the injected limb, sometimes involving the adjacent joint, fatigue.
Rare (≥1/10,000 to <1/1,000): Lymphadenopathy, thrombocytopenia, anaphylactic reactions, anaphylactoid reactions (including urticaria), allergic reactions (including pruritus), collapse or shock-like state (hypotonic-hyporesponsive episode), bronchitis, apnoea, rash, angioedema, swelling of the entire injected limb, extensive swelling reactions, injection site mass, injection site vesicles.
Very rare (<1/10,000): Appetite lost, Convulsions (with or without fever), dermatitis.
OVERDOSE: No cases of overdose reported.
Version: IFX-H/API/IN updated on 10 May 2023.
Registered medical practitioners can refer company website www.gsk-india.com/product-prescribing-information.aspx for full Product Information.
Please report adverse events with any GSK product to the company at india.pharmacovigilance@gsk.com
For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website: india-pharma.gsk.com/en-in/products/prescribing-information/ for Full Product Information. Please report adverse events with any GSK product to the company at india.pharmacovigilance@gsk.com. ©2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).