Managing pain and fever associated with childhood vaccination

Case scenario

Mr and Mrs Soe come into your pharmacy pushing young Edwin in his pram. Edwin is due for his 6-month vaccinations and has an appointment at his GP coming up this week. The Soe family want to get ‘the best pain and fever medicine they can, because after Edwin’s 4-month vaccinations he was quite upset and had a little bit of a fever afterwards (38.1 ºC)’.

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Introduction

Active immunisation uses vaccines to stimulate the immune system.¹ In turn, after the administration of vaccines that contain one or more immunogens, the immune system can react to a toxin or pathogen more effectively, helping prevent or reduce the severity of disease.¹ Vaccines may induce antibody production by B lymphocytes, that can bind specifically to a toxin or pathogen.¹ They may also boost numbers of killer cells such as CD8⁺ T cells to kill infected cells, or they may increase CD4⁺ T cells to help more efficiently ‘clear out’ infected cells.¹

Regardless of each vaccine’s mechanism of action, immunity after active immunisation generally lasts for months to many years.² How long the immune response lasts depends on the nature of the vaccine, the type of immune response (antibody or T-cell) and host factors.¹ Because of this, inducing the desired immune response may require a series of vaccine doses.²

The Australian Immunisation Handbook provides clinical guidelines about using vaccines safely and effectively. It outlines the vaccines recommended for children and adults following an evidence-based approach.² The National Immunisation Program schedule provides a guide to the recommended vaccines and their schedule (See Table 1).²

Case scenario

Edwin’s parents explain that he has kept up to date with all his vaccines so far and has no other health concerns. His 6-month vaccinations are being given in 3 days’ time. Looking at the vaccination schedule, you note that the upcoming vaccination will include diphtheria, tetanus, pertussis (DTP); hepatitis B; polio and Haemophilus influenzae type b (Hib). All these vaccinations are now available in one combined product.³ You also note that for Edwin’s 4-month vaccinations, he likely received two injections as opposed to the one, with pneumococcal also required at that time.²

Reactions to vaccinations are common,² and may include redness, swelling and soreness at the injection site, and sometimes a low-grade fever (38–38.5 °C).⁴ These reactions are usually mild and self-limiting.²

It is likely that Edwin’s low-grade fever and discomfort described by his parents after his 4-month injections were in line with the known common adverse effects associated with childhood vaccinations (see Table 2 ).²

Are prophylactic antipyretic/analgesic doses necessary?

According to the Australian Immunisation Handbook, it is not generally recommended to give a child prophylactic doses of paracetamol or ibuprofen prior to, or at the time of most vaccinations.² In fact, there is some evidence that interfering with the body’s natural immune response may lower the effectiveness of vaccines.⁵ In a randomised controlled trial published in the Lancet, researchers demonstrated that antibody response was significantly reduced in the group of healthy infants that received prophylactic paracetamol at the time of both the primary and booster vaccinations for DPT, Haemophilus influenzae and pneumococcal.⁵

The study concluded that ‘although febrile reactions significantly decreased, prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended, since antibody responses to several vaccine antigens were reduced’.⁵

In contrast to this advice, however, the immunisation guidelines now recommend a dose of paracetamol 30 minutes prior to the administration of a meningococcal B vaccine.² The vaccination schedule for healthy infants at low risk of disease recommends MenACWY vaccination at 12 months of age.² For infants at higher risk of disease, such as Aboriginal and Torres Strait Islander children, they are recommended to also have the meningococcal B vaccine at 2, 4, 6 (with specified risk conditions) and 12 months also. These vaccines have been shown to be associated with the AEFIs listed in Table 2.²

Due to these adverse effects, the Australian Immunisation Handbook suggests that an appropriate 15 mg/kg/dose of paracetamol should be administered 30 minutes prior to – or as soon as possible after – meningococcal B vaccination and can be followed by two more doses of paracetamol given 6 hours apart, regardless of whether the child has a fever.²

Responding to pain and fever

The Australian Immunisation Handbook mentions several strategies to use following vaccination. Immediate aftercare includes strategies such as distracting the infant by immediately changing the infant’s position, such as picking them up and placing them over the parent or caregiver’s shoulder and asking the adult to move around.²

The administration of analgesics or antipyretics following vaccination is rarely required if a child is eating, drinking, playing and happy.¹³ However, the handbook has recently been updated to include the use of either paracetamol or ibuprofen if a fever of >38.5 ^oC occurs with associated pain symptoms, or if there is moderate pain at the injection site.² This pain may be noticed if the infant is unsettled, and cries when the injection site is touched. These can be useful counselling points for parents or caregivers.

It is important to be aware of some of the common issues that arise with using these medicines.⁶ These include choosing the most appropriate agent to use; understanding the directions for use, including dose and dose-interval; and measuring the correct dose.⁶ There are also some common myths that parents and caregivers have surrounding the treatment of pain and fever in children that are discussed below.

Choosing the most appropriate option

Ibuprofen or paracetamol are considered first-line agents for pain with or without fever in children.⁷ For post-vaccination pain/fever in an infant 3 months and older, either agent would be appropriate.^7,8

There are some instances where one agent may, however, be preferred over the other. For example, for a child whose pain may be more inflammatory in nature – such as teething, sprain or post-vaccination pain – an anti-inflammatory agent such as ibuprofen may be considered an appropriate choice.^7,8

In an infant younger than 3 months of age, paracetamol would be the agent of choice, as ibuprofen is only recommended for use in children aged 3 months and older.

It is important to note that any infant younger than 3 months of age with fever should be referred to a general practitioner (GP).⁸

There are many caregivers who have been advised at certain times to administer both ibuprofen and paracetamol concurrently or to alternate doses.^9,10 This practice is usually not recommended, particularly for mild pain or mild pain associated with fever. Given that many caregivers can struggle with accurately dosing even one medication, recommending using two agents at the same time is not advised,^9,11 as complicating things with two agents could compound dose errors.

Understanding directions for use

Two studies have looked at Australian and/or New Zealand caregivers’ skills in being able to determine an appropriate dose of liquid over-the-counter medicines for their child.^9,11

Unfortunately, both of these studies highlighted serious flaws in caregivers’ abilities to recommend an appropriate weight-based dose of paracetamol or ibuprofen for their child. Paracetamol should be dosed at 15 mg/kg every 4–6 hours with a maximum of four doses in a 24-hour period.² Ibuprofen is dosed at 5–10 mg/kg every 6–8 hours with a maximum of three doses in 24 hours recommended.²

One study found almost 1 in 2 caregivers selected an incorrect dose of a liquid medicine (either paracetamol or ibuprofen) in a ‘mock fever scenario’ involving their child, despite the original packaging being available for them to look at.¹¹ More than 4% of the caregivers choosing paracetamol stated they would readminister the medication within 3 hours of the last dose, despite packaging indicating a 4–6-hour dose interval. Almost one-third of the caregivers who selected ibuprofen chose an incorrect dose interval of less than 6 hours.¹¹

Poor knowledge surrounding the dose interval for children’s ibuprofen doses was also found in another study in which two-thirds of caregivers incorrectly believed ibuprofen could be administered up to 4 times a day, instead of the maximum of 3 doses in a 24-hour period when used for a non-prescription dose.¹⁰

Measuring the correct dose

In the first study, 1 in 6 (16%) caregivers measured a dose that was outside a 10% error margin of the intended dose they stated for their child.¹¹ Another study found similar levels of liquid dosing accuracy, with 1 in 4 (24%) of doses deviating from what parents/caregivers had stated they would give.⁸ Of these deviations, 13% of doses deviated by more than 20% from the intended dose.⁹ This study also revealed that caregivers using medicine cups were more likely to measure an inaccurate dose in comparison to using a syringe.⁹ These findings further support that taking time to show parents/caregivers how to measure accurate doses and use accurate measuring devices is warranted.

Busting analgesic myths

Both parents and healthcare providers may have concerns about using non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen due to a perceived risk of gastrointestinal adverse effects. However, research consistently shows that when used short term as directed, over-the-counter doses of ibuprofen have a similar tolerability profile in paediatric pain and fever.^12,13 Both drugs are associated with a low risk of gastrointestinal (GI) adverse events in patients without contraindications or precautions.^12,13

A common misconception is that ibuprofen must be taken with food to minimise GI adverse effects. However, the evidence suggests that for over-the-counter doses of ibuprofen, there is no need to take doses with food, as they are well-tolerated regardless of when the dose is given, and food may even slightly delay gastric absorption. This is true even for children’s dosing.¹²

Finally, many people believe that an appropriate way to manage fever in children is to place the child in a cold or tepid bath or sponge them in cold water.⁶ Unfortunately, this practice can in fact make children very uncomfortable and cause them to shiver, which in turn can drive temperatures higher.⁶ Rather, guidelines recommend dressing children in enough clothing, so they are not too hot or cold. If they are shivering, it is recommended to add another layer of clothing or a blanket until they stop. A face washer or sponge soaked in warm water may be used to also keep them comfortable.⁶

Conclusion

Routine childhood vaccinations can sometimes be associated with mild adverse effects. Understanding how non-pharmacological strategies and medicines are used to treat pain or fever episodes in this patient cohort is essential in the delivery of evidence-based care by pharmacists. Pharmacists can further support parents and caregivers by addressing misconceptions related to medicines administration around the time of vaccination.

Key points

• Reactions to vaccinations in childhood are common, and may include redness, swelling and soreness at the injection site, and sometimes a low-grade fever. These reactions are usually mild and self-limiting.
• It is not generally recommended to give a child prophylactic doses of paracetamol or ibuprofen prior to, or at the time of, most vaccinations.
• Ibuprofen or paracetamol are considered first-line agents for pain with or without fever in children.
• Evidence suggests that for over-the-counter doses of ibuprofen, there is no need to take doses with food, as they are well-tolerated regardless of when the dose is given.

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References 

1. Siegrist CA. Vaccine Immunology. In: Plotkin SA, et al, eds. Plotkin’s Vaccines. 7th edn. Elsevier; 2018. p. 16–34.e7. 
2. Australian Technical Advisory Group on Immunisation. Australian Immunisation Handbook. Canberra: Australian Government Department of Health and Aged Care; 2024. 
3. National Centre for Immunisation Research and Surveillance (NCIRS), DTPa-HB-IPV-Hib Vaccine (Vaxelis® and Infanrix Hexa®), At: https://ncirs.org.au/ncirs-fact-sheets-faqs-and-other-resources/dtpa-hb-ipv-hib-vaccine-vaxelisr-and-infanrix-hexar
4. NPS MedicineWise. Treating my child’s pain or fever – paracetamol or ibuprofen? 2022.  At: http://www.nps.org.au/consumers/treating-my-child-s-pain-or-fever-paracetamol-or-ibuprofen
5. Prymula R, Siegrist CA, Chlibek R, et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet 2009;374(9698):1339–50. 
6. Royal Children’s Hospital Melbourne. Kids health information: fever in children. 2024  At: www.rch.org.au/kidsinfo/fact_sheets/fever_in_children/ 
7. Australian Medicines Handbook. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2023. 
8. Australasian College of Pharmacists. Management of acute pain and fever in children Brisbane: Australasian College of Pharmacists; 2023. At: www.acp.edu.au/education/guidelines/acute-pain-and-fever-in-children/ 
9. Hietbrink E, Bakshi R, Moles RJ. Australian caregivers’ management of childhood ailments. Int J Pharm Pract 2014;22(3):205–15. 
10. Arias D, Rawlinson C, Laing S, et al. Australian caregivers’ knowledge of and attitudes towards paediatric fever management. J Paediatr Child Health 2022;58(1):54–62. 
11. Emmerton L, Mampallil L, Kairuz T, et al. Management of children’s fever by parents and caregivers: practical measurement of functional health literacy. J Child Health Care2014;18(4):302–13. 
12. Tan E, Taylor DM, Ward B, et al. Comparison of acetaminophen (paracetamol) with ibuprofen for treatment of fever or pain in children younger than 2 years: a systematic review and meta-analysis. JAMA Netw Open 2020;3(10):e2022398. 
13. Kanabar DJ. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology 2017;25(1):1–9. 
14. Australian Government Department of Health and Aged Care. National immunisation program schedule. 2024. At: www.health.gov.au/resources/publications/national-immunisation-program-schedule?language=en 

Our author

Professor Rebekah Moles FPS, BPharm, DipHospPharm, PhD is a pharmacist and Professor at the Sydney Pharmacy School (University of Sydney).

Disclaimer

Vaccine administration should be in accordance with relevant legislation, the Australian Immunisation Handbook, and state-based conditions specific to the vaccine.