Hexacima (DTaP-IPV-HepB-Hib Vaccine)
Hexavalent combination vaccine for pediatric primary and booster immunization
Quick Facts About Hexacima
Key Takeaways About Hexacima
- Six-in-one protection: Hexacima protects against diphtheria, tetanus, pertussis, polio, hepatitis B, and Hib disease in a single injection, reducing the number of injections needed for infants
- Proven immunogenicity: Clinical trials involving over 5,700 infants demonstrated high seroprotection rates exceeding 96% for all six antigens after primary vaccination
- Flexible vaccination schedules: Compatible with both 2-dose and 3-dose primary schedules, allowing adaptation to different national immunization programs
- Well-established safety profile: The most common side effects are mild injection site reactions and transient irritability, which typically resolve within 1-3 days
- Can be co-administered: Hexacima can be given alongside other routine childhood vaccines, including pneumococcal, meningococcal, MMR, and rotavirus vaccines
What Is Hexacima and What Is It Used For?
Hexacima is a hexavalent combination vaccine that provides active immunization against six life-threatening infectious diseases: diphtheria, tetanus, pertussis (whooping cough), poliomyelitis, hepatitis B, and invasive disease caused by Haemophilus influenzae type b (Hib). It is indicated for primary and booster vaccination of infants and toddlers from 6 weeks of age.
Hexacima was developed by Sanofi Pasteur and received European Medicines Agency (EMA) marketing authorization in 2013. It represents a significant advancement in pediatric immunization by combining six essential antigens into a single 0.5 mL injection, thereby reducing the total number of injections required during the first years of life. This approach improves compliance with vaccination schedules and reduces the distress associated with multiple injections for both infants and their parents.
The vaccine contains inactivated or purified components of each pathogen. The diphtheria and tetanus components consist of detoxified toxoids that stimulate production of neutralizing antibodies. The pertussis component is acellular, containing purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which provides protection while minimizing the reactogenicity associated with older whole-cell pertussis vaccines. The poliovirus component contains inactivated strains of all three poliovirus types (Mahoney, MEF-1, and Saukett) grown on Vero cells.
The hepatitis B component consists of recombinant hepatitis B surface antigen (HBsAg) produced in yeast cells using recombinant DNA technology. The Haemophilus influenzae type b (Hib) component is a polysaccharide (polyribosylribitol phosphate, or PRP) conjugated to tetanus protein as a carrier, which enhances the immune response in young infants whose immune systems respond poorly to unconjugated polysaccharide antigens.
Hexavalent vaccines like Hexacima have become a cornerstone of childhood immunization programs worldwide. The World Health Organization (WHO) recommends that all infants receive vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, and Hib as part of routine immunization schedules. Prior to the availability of combination vaccines, achieving complete coverage required numerous separate injections, which contributed to parental hesitancy and suboptimal vaccination rates in some regions.
The six diseases targeted by Hexacima collectively caused millions of deaths annually before widespread vaccination. Diphtheria had a case fatality rate of 5-10%, neonatal tetanus killed an estimated 200,000 newborns per year, and pertussis remains a leading cause of vaccine-preventable deaths in infants under 6 months. Hepatitis B is responsible for approximately 820,000 deaths annually from cirrhosis and hepatocellular carcinoma, while Hib meningitis had a mortality rate of 2-5% even with antibiotic treatment.
What Should You Know Before Taking Hexacima?
Hexacima should not be given to infants with a known hypersensitivity to any vaccine component or who have experienced a serious adverse reaction after previous vaccination with diphtheria, tetanus, pertussis, polio, hepatitis B, or Hib vaccines. Vaccination should be postponed in case of acute moderate or severe febrile illness.
Contraindications
Hexacima is contraindicated in infants who have experienced a hypersensitivity reaction to the active substances, to any of the excipients, or to residual manufacturing substances such as glutaraldehyde, formaldehyde, neomycin, streptomycin, and polymyxin B. It is also contraindicated if the infant has experienced encephalopathy of unknown etiology within 7 days of a previous vaccination with a pertussis-containing vaccine.
If an infant has experienced any of the following events in temporal relation to a previous dose of pertussis-containing vaccine, the decision to administer further doses must be carefully considered: fever of 40.0°C or higher within 48 hours (not attributable to another identifiable cause), collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours, persistent and inconsolable crying lasting 3 hours or more within 48 hours, or seizures with or without fever within 3 days.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic reaction following vaccine administration. Epinephrine (adrenaline) and other appropriate resuscitation equipment should be immediately accessible during vaccination sessions.
Warnings and Precautions
Special caution is warranted in infants with a history of febrile seizures, as vaccination may temporarily increase the risk. Prophylactic antipyretic treatment (such as paracetamol) may be considered for infants with a history of febrile seizures or when fever is anticipated. However, routine prophylactic antipyretic use before vaccination is generally not recommended, as some studies suggest it may reduce the immune response to certain vaccine antigens, although the clinical significance of this remains uncertain.
Hexacima should be administered with caution to individuals with thrombocytopenia or a bleeding disorder, as intramuscular injection may cause bleeding. Firm pressure should be applied to the injection site (without rubbing) for at least 2 minutes. In patients receiving anticoagulant therapy, the vaccine may be administered subcutaneously if intramuscular injection could pose a risk, although the intramuscular route is preferred for optimal immunogenicity.
The immune response to Hexacima may be reduced in individuals receiving immunosuppressive therapy or those with immunodeficiency conditions. In such cases, vaccination should ideally be deferred until the immunosuppressive treatment is completed or the condition has resolved. However, individuals with chronic immunodeficiency, including HIV infection, should still be vaccinated even though the antibody response may be limited, as the potential benefit outweighs the risk.
Syncope (fainting) can occur following, or even before, any injection. Healthcare providers should have procedures in place to prevent injury from falls and manage vasovagal reactions. Although this is more commonly a concern in adolescents and adults, it should be considered, especially when vaccinating older toddlers.
Pregnancy and Breastfeeding
Hexacima is a pediatric vaccine and is not intended for use in adults, adolescents, or pregnant or breastfeeding women. It is indicated exclusively for infants and toddlers from 6 weeks of age. There are no studies evaluating the use of Hexacima during pregnancy or lactation, as the vaccine is not applicable to these populations.
It should be noted that vaccination of the infant with Hexacima is fully compatible with maternal breastfeeding. Breastfed infants can and should receive their vaccinations according to the recommended schedule. There is no evidence that breastfeeding interferes with the infant's immune response to vaccination, and breastfeeding may in fact provide additional immune support during the post-vaccination period.
How Does Hexacima Interact with Other Drugs?
Hexacima can be safely co-administered with most routine childhood vaccines. Clinical studies have demonstrated compatibility with pneumococcal conjugate vaccines, meningococcal vaccines, MMR, varicella, and rotavirus vaccines without clinically significant interference with immune responses.
One of the key advantages of combination vaccines like Hexacima is their compatibility with other vaccines in the childhood immunization schedule. Extensive clinical trial data supports the co-administration of Hexacima with a range of other vaccines, allowing healthcare providers to administer multiple vaccines during a single visit. This is an important consideration for maintaining high vaccination coverage and reducing the number of clinical visits required.
When co-administered with other injectable vaccines, Hexacima must be given at a different injection site. For infants, this typically means using both anterolateral thighs, with each vaccine injected into a separate thigh. The vaccine should never be mixed with other vaccines in the same syringe.
| Vaccine / Drug | Interaction Type | Recommendation |
|---|---|---|
| Pneumococcal conjugate vaccine (PCV13) | Compatible | Can be co-administered at different injection sites |
| Rotavirus vaccine | Compatible | Oral rotavirus vaccine can be given at the same visit |
| Meningococcal C conjugate vaccine | Compatible | Can be co-administered at different injection sites |
| MMR vaccine | Compatible | Can be co-administered during booster visits |
| Varicella vaccine | Compatible | Can be co-administered at different injection sites |
| Immunosuppressive agents | Reduced response | May reduce immune response; defer if possible or monitor antibody levels |
| Immunoglobulins | Potential interference | Do not administer simultaneously; consult guidelines for timing |
| Paracetamol (prophylactic) | May reduce response | Routine prophylactic use not recommended; use for managing fever post-vaccination |
Co-Administration Data
In pivotal clinical trials, Hexacima was co-administered with Prevenar 13 (pneumococcal conjugate vaccine) in over 1,500 infants. The results demonstrated that co-administration did not affect the seroprotection rates for any of the six Hexacima antigens or for the pneumococcal serotypes. Similarly, co-administration with RotaTeq or Rotarix (rotavirus vaccines) showed no clinically meaningful interference with immune responses.
Studies evaluating co-administration with meningococcal vaccines, including MenC conjugate and MenACWY vaccines, also confirmed immunological compatibility. The booster dose of Hexacima can be co-administered with MMR vaccine and varicella vaccine at 11-18 months of age without compromising the immune response to any of the vaccines.
Infants who are receiving immunosuppressive therapy (such as corticosteroids, cytotoxic agents, or biological immunomodulators) may have a diminished immune response to Hexacima. In these cases, the decision to vaccinate should be made by a specialist, weighing the potential benefit of vaccination against the likelihood of an adequate immune response. Serological testing to confirm seroconversion may be appropriate in immunocompromised patients.
What Is the Correct Dosage of Hexacima?
Hexacima is given as a 0.5 mL intramuscular injection. The recommended primary schedule consists of two or three doses given at least one month apart, starting from 6 weeks of age, followed by a booster dose at least 6 months after the last primary dose. The exact schedule follows national immunization program recommendations.
Hexacima is supplied as a 0.5 mL pre-filled syringe containing a ready-to-use suspension for intramuscular injection. The vaccine should be administered into the anterolateral thigh in infants, as this is the preferred injection site for intramuscular vaccines in children under 2 years of age. The vaccine should not be injected into the gluteal region, as absorption may be impaired, and the sciatic nerve could be at risk.
| Schedule Type | Primary Series | Booster Dose | Example Schedule |
|---|---|---|---|
| 3-dose primary + booster (3+1) | 3 doses at least 4 weeks apart | 1 dose at least 6 months after 3rd primary dose | 2, 3, 4 months + booster at 11-13 months |
| 2-dose primary + booster (2+1) | 2 doses at least 8 weeks apart | 1 dose at least 6 months after 2nd primary dose | 3, 5 months + booster at 11-13 months |
| WHO EPI schedule | 3 doses at 6, 10, and 14 weeks | Booster in 2nd year of life recommended | 6, 10, 14 weeks + booster at 15-18 months |
Infants (Primary Vaccination)
The primary vaccination schedule depends on national recommendations and can follow either a 2-dose or 3-dose regimen. In a 3+1 schedule, three primary doses of 0.5 mL each are administered at intervals of at least 4 weeks, typically beginning at 2 months of age (e.g., at 2, 3, and 4 months or 2, 4, and 6 months). In a 2+1 schedule, two primary doses of 0.5 mL are given at least 8 weeks apart, often at 3 and 5 months of age.
The first dose can be administered as early as 6 weeks (42 days) of age. This is particularly relevant in regions where early immunization is critical due to high disease prevalence. There is no strict upper age limit specified in the product labeling for the primary series, although it is primarily intended for infants in the first year of life.
Booster Vaccination
A booster dose of 0.5 mL should be administered at least 6 months after the last primary dose, typically in the second year of life (between 11 and 18 months of age, depending on the national schedule). The booster dose is essential to ensure long-lasting immunity, as antibody levels against some antigens, particularly pertussis and Hib, may decline after primary vaccination alone.
If the primary series is delayed or interrupted for any reason, it is not necessary to restart the series. Subsequent doses should be given at the earliest opportunity, maintaining the minimum intervals between doses. The vaccine schedule is flexible enough to accommodate catch-up vaccination in infants and toddlers who have not been vaccinated on time.
Premature Infants
Premature infants, including those born at less than 28 weeks of gestation, should be vaccinated according to their chronological age, not their corrected gestational age. Studies have shown that premature infants develop adequate immune responses to Hexacima, although antibody levels may be somewhat lower than in full-term infants. The booster dose is particularly important in this population to ensure sufficient long-term protection.
Very premature infants (born at or before 28 weeks of gestation) may be at increased risk for apnea episodes following vaccination. Respiratory monitoring for 48-72 hours after the first and second vaccination doses is recommended for these infants, particularly if they have a history of respiratory immaturity. Despite this precaution, vaccination should not be withheld or delayed, as the potential consequences of the diseases targeted are far more severe.
Missed Dose
If a scheduled dose of Hexacima is missed, it should be administered as soon as possible. There is no need to restart the entire vaccination series if a dose is delayed. The minimum intervals between doses should be maintained: at least 4 weeks between primary doses in a 3+1 schedule, at least 8 weeks between primary doses in a 2+1 schedule, and at least 6 months between the last primary dose and the booster.
Healthcare providers should use every opportunity to check vaccination status and administer any missing doses. Catch-up vaccination with Hexacima can be undertaken for children who have not completed their primary or booster immunization, provided they are still within the appropriate age range as defined by national guidelines.
Overdose
Cases of overdose with Hexacima have not been specifically reported in the medical literature. If an excessive dose were to be administered, the expected effects would be an increase in local and systemic reactions consistent with the known side-effect profile of the vaccine. No specific antidote exists. In the unlikely event of an overdose, the patient should be monitored for any adverse reactions, and supportive treatment should be provided as necessary.
If an infant inadvertently receives two doses in a single visit, the event should be documented and reported through the appropriate pharmacovigilance channels. The infant should continue the scheduled vaccination series as planned, counting the inadvertent extra dose as one of the planned doses if timing permits.
What Are the Side Effects of Hexacima?
The most common side effects of Hexacima are injection site reactions (pain, redness, swelling), irritability, crying, drowsiness, and decreased appetite. These effects are generally mild to moderate and resolve spontaneously within 1-3 days. Serious adverse reactions are rare.
The safety profile of Hexacima has been extensively evaluated in clinical trials involving over 5,700 infants and in extensive post-marketing surveillance covering millions of doses administered worldwide. Like all vaccines, Hexacima can cause side effects, although not everybody experiences them. The majority of reported adverse reactions are mild and self-limiting, reflecting the expected immune response to vaccination.
Parents and caregivers should be informed about possible reactions before vaccination and advised on appropriate management, including the use of age-appropriate doses of paracetamol for managing fever and discomfort. It is important to emphasize that the benefits of protection against six potentially life-threatening diseases far outweigh the risks of these generally mild and temporary side effects.
Below is a comprehensive breakdown of side effects categorized by their frequency of occurrence, based on clinical trial data and post-marketing surveillance reports.
Very Common
- Injection site pain, tenderness
- Injection site redness (erythema)
- Injection site swelling (induration)
- Irritability, fussiness
- Crying (including inconsolable crying)
- Drowsiness, sleepiness
- Decreased appetite
- Fever (temperature 38.0°C or above)
Common
- Injection site induration
- Vomiting
- Diarrhea
- High fever (temperature above 39.0°C)
Uncommon
- Extensive injection site swelling (more than 50 mm)
- Injection site nodule
- Skin rash, urticaria (hives)
- Very high fever (temperature above 40.0°C)
Rare / Very Rare
- Hypotonic-hyporesponsive episode (HHE)
- Febrile seizures
- Anaphylactic reaction
- Apnea in very premature infants (born at ≤28 weeks gestation)
- Extensive limb swelling involving the entire vaccinated limb
Seek emergency medical care immediately if the infant develops signs of an allergic reaction (difficulty breathing, facial swelling, widespread hives), high-pitched or unusual crying that persists for more than 3 hours, seizures, or a hypotonic-hyporesponsive episode (sudden limpness, paleness, and unresponsiveness). These reactions are extremely rare but require urgent medical evaluation.
It is important to note that many studies have investigated the long-term safety of hexavalent vaccines. Large-scale pharmacoepidemiological studies, including those conducted by the Brighton Collaboration and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), have not identified any new safety signals beyond those identified in pre-authorization clinical trials. The benefit-risk balance of Hexacima remains strongly positive.
Injection site reactions typically peak within the first 24-48 hours and resolve within 2-3 days. Localized swelling and redness at the injection site are normal immune responses and do not indicate infection. Parents should be reassured that these reactions do not require antibiotic treatment. Cool compresses and age-appropriate analgesics (paracetamol) can be used for comfort if needed.
How Should You Store Hexacima?
Hexacima must be stored in a refrigerator at 2°C to 8°C and must not be frozen. The vaccine should be kept in the outer carton to protect it from light. Once removed from refrigeration, the vaccine should be used promptly.
Proper storage is critical to maintaining the potency and safety of Hexacima. The vaccine contains biological components that are sensitive to both heat and freezing, and improper storage can render the vaccine ineffective without any visible change in its appearance. Healthcare facilities should maintain a rigorous cold chain management system to ensure vaccine quality from the point of manufacture through to the point of administration.
Hexacima should be stored at 2°C to 8°C (36°F to 46°F) in a pharmaceutical-grade refrigerator with continuous temperature monitoring. The vaccine must not be frozen under any circumstances, as freezing destroys the aluminum adjuvant structure and can denature the protein antigens, significantly reducing the vaccine's immunogenicity. If the vaccine has been accidentally frozen, it must be discarded.
The pre-filled syringe should be kept in the outer carton to protect it from light, as some vaccine components may be light-sensitive. Before administration, the vaccine should be allowed to reach room temperature and should be gently shaken to ensure a homogeneous suspension. After shaking, the vaccine should appear as a whitish, turbid suspension. If the vaccine contains particles, appears discolored, or does not resuspend after shaking, it should not be used.
The shelf life of Hexacima when stored correctly is 3 years from the date of manufacture. The expiry date is printed on the carton and syringe label and should always be checked before administration. Expired vaccines must never be administered and should be disposed of according to local regulations for biological waste.
Temperature: 2°C to 8°C (refrigerator). Do not freeze. Keep in original carton protected from light. Shelf life: 3 years. Check expiry date before use. Discard if frozen, discolored, or contains particles that do not resuspend.
What Does Hexacima Contain?
Each 0.5 mL dose of Hexacima contains six active antigens: diphtheria toxoid, tetanus toxoid, pertussis antigens (PT and FHA), inactivated poliovirus types 1-3, hepatitis B surface antigen, and Hib polysaccharide conjugated to tetanus protein, all adsorbed onto aluminum hydroxide as adjuvant.
Active Ingredients
Each 0.5 mL dose of Hexacima contains the following active substances:
- Diphtheria toxoid: Not less than 20 IU (International Units), adsorbed on aluminum hydroxide
- Tetanus toxoid: Not less than 40 IU, adsorbed on aluminum hydroxide
- Bordetella pertussis antigens: Pertussis toxoid (PT) 25 micrograms and filamentous haemagglutinin (FHA) 25 micrograms, adsorbed on aluminum hydroxide
- Inactivated poliovirus type 1 (Mahoney): 40 D-antigen units
- Inactivated poliovirus type 2 (MEF-1): 8 D-antigen units
- Inactivated poliovirus type 3 (Saukett): 32 D-antigen units
- Hepatitis B surface antigen (rDNA): 10 micrograms, produced in yeast cells (Hansenula polymorpha) by recombinant DNA technology, adsorbed on aluminum hydroxide
- Haemophilus influenzae type b polysaccharide (PRP): 12 micrograms, conjugated to tetanus protein (22-36 micrograms), adsorbed on aluminum hydroxide
Excipients and Adjuvant
The vaccine contains aluminum hydroxide (0.6 mg Al) as an adjuvant, which enhances the immune response to the vaccine antigens. Other excipients include disodium hydrogen phosphate, potassium dihydrogen phosphate, trometamol, sucrose, essential amino acids (including L-phenylalanine), and water for injection.
Residual traces of glutaraldehyde, formaldehyde, neomycin, streptomycin, and polymyxin B may be present from the manufacturing process. These substances are used during production and purification of the vaccine components and are reduced to trace amounts in the final product. Individuals with known allergies to these substances should be assessed before vaccination, although true allergic reactions to trace amounts in vaccines are extremely rare.
The vaccine does not contain thiomersal (thimerosal) or any other mercury-based preservative. This is consistent with the global trend toward preservative-free, single-dose presentations of pediatric vaccines, which eliminates any theoretical concern about mercury exposure from vaccine preservatives.
Frequently Asked Questions About Hexacima
References
- European Medicines Agency (EMA). Hexacima Summary of Product Characteristics. Last updated 2024. Available at: www.ema.europa.eu/en/medicines/human/EPAR/hexacima
- World Health Organization (WHO). WHO Position Paper on Diphtheria, Tetanus, Pertussis Vaccines. Weekly Epidemiological Record. 2017;92(12):129-148.
- World Health Organization (WHO). WHO Position Paper on Hepatitis B Vaccines. Weekly Epidemiological Record. 2017;92(27):369-392.
- World Health Organization (WHO). WHO Position Paper on Haemophilus influenzae type b Conjugate Vaccines. Weekly Epidemiological Record. 2013;88(39):413-428.
- World Health Organization (WHO). WHO Position Paper on Polio Vaccines. Weekly Epidemiological Record. 2022;97(25):277-300.
- Immunisation Advisory Centre (IMAC). Hexavalent Vaccines: A Review. 2023.
- Vesikari T, et al. Immunogenicity and safety of a hexavalent vaccine (DTaP-IPV-HB-PRP-T) administered in a 2-dose or 3-dose primary vaccination schedule followed by a booster dose. Vaccine. 2017;35(27):3437-3445.
- Chlibek R, et al. Immunogenicity and safety of Hexacima co-administered with Prevenar 13 and Rotarix: A randomized clinical trial. The Lancet Infectious Diseases. 2014;14(10):935-945.
- Centers for Disease Control and Prevention (CDC). Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger, United States, 2024.
- British National Formulary for Children (BNFc). Hexacima. National Institute for Health and Care Excellence (NICE), 2024.
Editorial Team
This article was written, reviewed, and fact-checked by the iMedic Medical Editorial Team, specialists in pediatrics, immunology, and infectious disease. All content follows international guidelines from the WHO, EMA, and CDC and adheres to the iMedic Editorial Standards.
Last medical review: . Next scheduled review: . Meet our medical team.