Previous changes

May 2021 — minor update. A recommendation that Avaxim should be used with caution in people with phenylketonuria has been added to this topic in line with the manufacturer's Summary of Product Characteristics.

January 2021 — minor update. A typographical error has been corrected.

August 2020 — minor update. Broken URL link updated.

October 2019 — reviewed. A literature search was conducted in October 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

December 2016 — minor update. Information added on concomitant administration of Havrix®.

January to April 2014 — reviewed. A literature search was conducted in January 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made.

September 2013 — minor update to the text to reflect current recommendations regarding metoclopramide.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and Healthcare products Regulatory Agency. Prescriptions have been updated to reflect the revised dosing. 

September 2010 — minor update. Additional information has been included in the Prescribing information section. 

April to August 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 May 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 May 2024.

Economic appraisals

No new economic appraisals relevant to England since 1 May 2024.

Systematic reviews and meta-analyses

No new systematic review or meta-analyses since 1 May 2024.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 May 2024.

New policies

No new national policies or guidelines since 1 May 2024.

New safety alerts

No new safety alerts since 1 May 2024.

Changes in product availability

No changes in product availability since 1 May 2024.

Basis for recommendation

The information on case definitions for hepatitis A is based on expert opinion in the UK Health Security Agency (UKHSA) guideline Public health control and management of hepatitis A [UKHSA, 2024a].

Basis for recommendation

The information on the clinical features of hepatitis A infection is based on guidance from the British Association of Sexual Health and HIV (BASHH) National Guidelines for the Management of the Viral Hepatitides [BASHH, 2017], the UK Health Security Agency Public health control and management of hepatitis A [UKHSA, 2024a], and the National Travel Health Network and Centre Hepatitis A [NaTHNaC, 2023]; the World Health Organization factsheet Hepatitis A [WHO, 2023], the BMJ Best Practice guideline Hepatitis A [BMJ Best Practice, 2024], and expert opinion in review articles [Randazzo, 2020; Gabrielli, 2023].

Basis for recommendation

The recommendations on investigations to confirm a diagnosis of hepatitis A are largely based on expert opinion in the British Association of Sexual Health and HIV (BASHH) National Guidelines for the Management of the Viral Hepatitides [BASHH, 2017], the UK Health Security Agency guidelines Public health control and management of hepatitis A [UKHSA, 2024a], and UK Standards for Microbiology Investigations: Hepatitis A virus acute infection serology [PHE, 2019], the Oxford Textbook of Medicine [Alexander, 2020], the BMJ Best Practice guideline Hepatitis A [BMJ Best Practice, 2024], guidance from the US Centres for Disease Control and Prevention Clinical Screening and Diagnosis for Hepatitis A [CDC, 2024], and expert opinion in review articles [Langan, 2021; Migueres, 2021; Dionne-Odom, 2022].

Hepatitis serology requests

• The recommendation to state any suspicion of hepatitis A on the laboratory request form when ordering hepatitis serology is based on the opinion of a previous expert reviewer of this CKS topic. Hepatitis A may not be routinely included in hepatitis serology screens in all laboratories in the UK, so it should be specifically requested if required. Additionally, as the clinical features of acute hepatitis A cannot readily be distinguished from other forms of acute hepatitis, and some people may have co-infection with other hepatitis viruses or HIV, a full hepatitis screen may be advised [BASHH, 2017; British Liver Trust, 2023].

Repeat serology

• The recommendation to repeat serology if the person has had an initial negative result but is in the first week of symptoms to exclude a false-negative result is based on guidance from the UKHSA [UKHSA, 2024a] — timing of repeat sample is not specified in this guidance. Expert opinion in a hepatitis A review article [Cuthbert, 2001] and a previous expert reviewer of this CKS topic recommend repeating HAV-IgM levels 1–2 weeks later, if the person has had an initial negative result but is in the first 7–10 days of symptoms.

Basis for recommendation

The information about the differential diagnosis of hepatitis A is based on expert opinion in the Oxford Textbook of Medicine [Alexander, 2020] and the BMJ Best Practice guideline Hepatitis A [BMJ Best Practice, 2024].

Who should be offered vaccination for hepatitis A?

• Vaccination is indicated for people considered to be at high risk of acquiring hepatitis A infection, and/or those at the highest risk of complications, including:
  • People (aged one year and older) travelling to or going to reside in areas of high or medium prevalence (and occasionally during outbreaks in lower prevalence areas).
    • The risk of disease in children under 1 year old is low and vaccines are not licensed for use at this age.
    • Vaccine should preferably be given at least 2 weeks before departure, but may still provide some protection when given up to the day of departure.
    • Country-specific information on the risk of hepatitis A can be found on the Country Information pages on the National Travel Network Centre website.
  • People with chronic liver disease (including hepatitis B or C infection) — the risk of complications is increased.
  • People receiving plasma-derived clotting factors to treat haemophilia.
  • People who inject drugs.
  • Men who have sex with men.
  • People at occupational risk including:
    • Laboratory workers who may be exposed to hepatitis A in their work.
    • Staff and residents of some large residential institutions such as those for people with learning difficulties.
    • Sewage workers and others exposed to raw sewage.
    • People who work with primates.
  • For further information, see the section on risk factors for risk factors.
• Hepatitis A vaccination may also be considered under certain circumstances such as:
  • Food packagers and handlers — routine vaccination in this group is not indicated in the UK. Where a case or outbreak occurs, advice should be sought from the local Health Protection Team.
  • Staff in day care facilities — where well-defined community outbreaks, such as in a pre-school nursery have occurred, advice on the need for immunisation of staff and children should be discussed with the local Health Protection Team.
  • Healthcare workers — routine immunisation is not indicated.
• The usual schedule for monovalent hepatitis A vaccines is a single dose (provides protection for up to 12 months) and then a booster dose 6-12 months later if the person remains at long-term risk of contracting hepatitis A.
  • Some vaccines combine hepatitis A with other antigens (typhoid or hepatitis B) and may require different schedules.
  • Pregnancy and breast feeding are not contraindications to receiving the hepatitis A vaccine where clinically indicated.
  • For more detailed information on the available hepatitis A vaccines, see the section on Prescribing information. Combined hepatitis A and B vaccines should be considered for people at risk of both infections — for further details, see the CKS topic on Hepatitis B.

What advice should I give to people at high risk of hepatitis A infection?

• Advise people at high risk of acquiring hepatitis on immunisation and additional measures to reduce risk:
  • People engaging in activities that pose a high risk of infection via the faecal-oral route should be advised to:
    • Practice safe sex and maintain high standards of hygiene during sex to reduce the risk of sexual acquisition/transmission.
    • Avoid reusing/sharing equipment for injecting or snorting drugs.
    • Thoroughly wash their hands before food preparation and eating.
    • Ensure good personal hygiene.
  • People travelling to moderately or highly endemic areas should be advised to:
    • Practice good personal hygiene — hands should be thoroughly washed after visiting the toilet, changing nappies, and always before preparing or eating food.
    • Avoid food and water that is potentially contaminated by human faeces — in particular, foods grown close to the ground (such as strawberries and salad vegetables) and undercooked or raw shellfish. 
    • Avoid drinking untreated water including ice cubes and use bottled water to brush teeth.
  • People at occupational risk of infection should be advised to use appropriate protective gloves, boots, and face protection as required within their individual roles.
• For more information on:
  • How people with hepatitis A can reduce the risk of transmission to others, see the section on Information and advice.
  • The prevention of food and water-borne diseases, see the National Travel Health Network and Centre (NaTHNaC) website.

How should I manage a person with confirmed or probable hepatitis A infection?

• Admit any person with hepatitis A infection to hospital if they are severely unwell, for example, with vomiting, dehydration, or signs of hepatic decompensation.
• If hospital admission is not required, provide supportive symptomatic care as required:
  • Advise the person to rest when necessary, and stay hydrated.
  • If pain relief is required, options include:
    • Ibuprofen — prescribe with caution in mild to moderate hepatic impairment and avoid in severe hepatic impairment.
    • Paracetamol — caution is advised with the use of paracetamol in people with acute hepatitis due to increased risk of toxicity — avoid if possible.
    • Weak opioids (such as codeine) — prescribe with caution in mild liver impairment and avoid in severe hepatic impairment (due to enhanced sedative effects and reduced drug clearance).
    • For further information, see the CKS topic on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues.
  • If treatment of nausea is required, options include:
    • Metoclopramide (for people aged over 20 years for a maximum duration of 5 days of treatment) or cyclizine, if liver impairment is mild.
    • For further information, see the section on Prescribing.
  • If treatment of itch is required, options include:
    • Simple measures (such as maintaining a cool, well-ventilated environment, wearing loose clothing, and avoiding hot baths or showers).
    • Chlorphenamine at night — avoid in severe liver impairment.
    • For further information, see the section on Prescribing.
  • Seek specialist advice on the choice and dosage of analgesic, anti-emetic, or anti-pruritic if the person has more severe hepatic impairment or symptoms are difficult to manage.
  • Withold potentially hepatotoxic drugs – seek specialist advice if unsure.
• Notify the local Health Protection Unit (HPU) promptly to facilitate appropriate surveillance, contact tracing, and initiation of preventative measures for close contacts. 
  • If an outbreak is suspected, or the person is a food handler or staff in residential care, notify the HPU immediately 
  • On confirmation of infection the health protection team will ask the person to complete a Hepatitis A: case questionnaire.
• Provide the person with information and advice about hepatitis A. In particular, advise them to:
  • Avoid drinking alcohol, as this can increase the risk of liver damage.
  • Avoid work, school, or nursery until they are no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms; such as fatigue, nausea, or fever, if there is no history of jaundice).
  • Take steps to minimize the risk of transmission to partners and contacts. The person and all close contacts should:
    • Ensure thorough hand washing after using the toilet, including supervising young children who may have difficulty with personal hygiene.
    • Wash their hands immediately after changing nappies or helping with child toileting (including handling a potty).
    • Ensure good general personal hygiene.
    • Avoid handling food, if possible, or ensure thorough hand washing before food preparation, for contacts of cases.
    • Avoid unprotected sexual intercourse, including oro-anal and oro-genital contact, until the person is no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice).
    • Avoid sharing needles and other drug paraphernalia. For information on managing intravenous drug users, see the CKS topic on Opioid dependence.
• For pregnant women with acute hepatitis A infection, inform the midwifery/obstetric team of the diagnosis and advise the woman that:
  • Infection in early pregnancy is not thought to increase the risk of congenital malformation in the infant.
  • They may be at increased risk of preterm labour if infection occurs in the second or third trimester and should seek urgent medical advice if symptoms develop or they are concerned.
  • Breastfeeding is not known to pose a specific risk — thorough hand washing and personal hygiene should be maintained.
• Advise the person that patient information is available from:
  • The NHS Hepatitis A.
  • The British Liver Trust Hepatitis A.
  • UK Health Security Agency Hepatitis A information sheet.
• Consider referring the person to a:
  • Genito-urinary medicine department (or other specialist sexual health service), if screening for sexually transmitted infections is appropriate.
  • Drug rehabilitation agency (if appropriate).
• Follow-up at least every 1 to 2 weeks:
  • Consider more frequent follow-up if the person is symptomatic, and/or has jaundice, and depending on the results of liver function tests).
  • Repeat liver function tests until amino-transferase levels are normal (usually 4–12 weeks).
  • Seek specialist advice if the person has significantly abnormal liver function tests or coagulation screen, or if liver function appears to be worsening.
  • Advise the person to seek medical attention if symptoms worsen (particularly if they include vomiting and dehydration) and to be aware of the signs of hepatic decompensation (change in personality or level of consciousness).
  • Admit the person to hospital if they become severely unwell.

How do I manage someone who has been in contact with a person with hepatitis A?

If a person presents who has been in contact with someone with known hepatitis A infection:

• Contact the local Health Protection Unit (HPU) immediately, who will advise on further management if the person has not previously received the hepatitis A vaccine. This may include giving hepatitis A vaccination and/or arranging for the administration of human normal immunoglobulin, depending on the timing and circumstances of contact, as well as other factors including the person's age and co-morbidities.

What types of hepatitis A vaccine are available?

• There are several hepatitis A vaccines that are licensed for use in the UK. All are inactivated, and prepared from different strains of the hepatitis A virus:
  • Avaxim^®— age range 16 years or older.
  • Avaxim Junior^®— age range 1 to 15 years.
  • Havrix Monodose^®— age range 16 years or older.
  • Havrix Junior Monodose^®— age range 1 to 15 years.
  • Vaqta^®— age range 18 years or older.
  • Vaqta Paediatric^®— age range 1 to 17 years.
• There are also combined hepatitis A and B vaccines:
  • Twinrix Adult^®— age range 16 years or older.
  • Twinrix Paediatric^®— age range 1 to 15 years.
  • Ambirix^® (paediatric formulation) — age range 1 to 15 years.

[NaTHNaC, 2023; BNF, 2024; UKHSA, 2024b]

What is the immunization schedule for the hepatitis A vaccine?

• The hepatitis A monovalent vaccine is given in two doses, 6–12 months apart.
  • If the second dose has been missed there is no need to restart immunization. Give the second dose as soon as possible after the missed dose.
  • Antibodies may not be detectable for 12–15 days following administration of monovalent hepatitis A vaccine. However, the vaccine may provide some protection before antibodies can be detected, and vaccination up to the day of departure may be beneficial.
  • Immunity theoretically persists for more than 20 years after the second dose. A further booster dose is recommended at 25 years for people at ongoing risk of infection. Specialist advice should be sought for people with altered immune responses — an earlier booster may be indicated.
• The schedule for the combined hepatitis A and B vaccine varies between products:
  • Twinrix^® is given in three doses, at 0, 1, and 6 months.
    • If Twinrix^® is given as a rapid schedule (on days 0, 7, and 21), a booster dose is needed at 1 year.
  • Ambirix^® is given in two doses, 6–12 months apart.
• For travellers, the first dose of hepatitis A single or combined vaccine should ideally be given at least 2 weeks before travelling (but can be given up to the day of departure).
• Hepatitis A-containing vaccines can be given at the same time as other vaccines such as hepatitis B, MMR, MenACWY, Td/IPV and other travel vaccines. The vaccines should be given at a separate site, preferably in a different limb. If given in the same limb, they should be given at least 2.5 cm apart — the site at which each vaccine was given should be documented.
• Shortages of monovalent hepatitis A vaccine have occurred previously — information on vaccine supply is available from the UK Health Security Agency: Vaccine Update. 

[NaTHNaC, 2023; UKHSA, 2024b]

What hepatitis A vaccination schedule should be used for people with HIV?

• People with immunosuppression and HIV can be given hepatitis A containing vaccines. However, seroconversion rates and antibody titre may be lower depending on CD4 count at the time of immunisation.
  • Seek specialist advice — re-immunisation may be indicated.

[UKHSA, 2024b]

When is the hepatitis A vaccine contraindicated?

• Do not give hepatitis A vaccine if the person:
  • Is acutely unwell — postpone vaccination until fully recovered.
    • Minor illness without fever or systemic upset (such as a cold) is not an indication to postpone vaccination.
  • Has experienced a confirmed anaphylactic reaction to a previous dose of hepatitis A vaccine, or any component of the vaccine.
    
    • Avaxim^®, Twinrix^®, and Ambirix^® should not be given to people who have had a confirmed anaphylactic reaction to neomycin.
    • VAQTA® should not be given to people who have had a confirmed anaphylactic reaction to neomycin or formaldehyde.
• Avaxim® and Havrix^® should be used with caution in people with phenylketonuria as they contain phenylalanine.

[EMC, 2022a; EMC, 2022b; EMC, 2023a; EMC, 2023b; EMC, 2023c; UKHSA, 2024b]

How should I administer the hepatitis A vaccine?

• Obtain written or verbal consent at the time of vaccination — ensure that there are no contraindications.
• Check that the vaccine is correct and has not expired. Only clean the site of application with soap and water if it is visibly dirty.
• For adults and children older than 1 year of age, administer the vaccine by intramuscular injection into the deltoid muscle or the anterolateral aspect of the thigh — anterolateral thigh is the preferred site in infants and young children.
• If the person has a bleeding disorder, the subcutaneous route may be used to reduce the risk of bleeding.
• Record the site of administration. If an additional vaccine is required on the same day, use separate limbs if possible, or inject at sites at least 2.5 cm apart in the same limb.
• Observe for immediate adverse drug reactions.

[UKHSA, 2013; UKHSA, 2023; BNF, 2024; UKHSA, 2024b]

What are the adverse effects of the hepatitis A vaccine?

• Adverse effects of hepatitis A vaccines are usually mild and only occur within the first few days following immunisation. The most common reactions are mild, transient tenderness, swelling, and erythema at the injection site. A small, painless nodule may form at the injection site — this usually disappears and is of no consequence.
• General symptoms (such as fever, malaise, fatigue, headache, dizziness, nausea, and loss of appetite) are also reported less frequently.

[NaTHNaC, 2023; UKHSA, 2024b]

Contraindications and cautions

• Metoclopramide should not be used in people with:
• • Gastrointestinal obstruction, perforation or haemorrhage or recent gastrointestinal surgery.
  • Confirmed or suspected pheochromocytoma, due to the risk of severe hypertensive episodes.
  • History of neuroleptic or metoclopramide-induced tardive dyskinesia.
  • Epilepsy (increases crisis frequency and intensity).
  • Parkinson's disease.
• Metoclopramide should be used with caution in:
  • Liver dysfunction — metoclopramide can be used in people whose metabolic and synthetic function is unaffected (such as in mild hepatitis). However, seek specialist advice before using metoclopramide in people with more severe hepatic impairment, as reduced clearance may increase the risk of gynaecomastia and extrapyramidal adverse effects. The dose should be reduced by 50% in people with severe hepatic impairment.
  • Renal impairment — metoclopramide and its metabolites are predominately excreted via the kidneys. In people with severe renal impairment (eGFR less than 30 mL/minute/1.73 m²), avoid metoclopramide or use a reduced dose. Accumulation of metoclopramide increases the risk of extrapyramidal adverse effects.
  • Children, young people and the elderly — neurological effects such as short-term extrapyramidal adverse effects have been reported. This risk is higher in children, although tardive dyskinesia was reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The European Medicines Agency recommended that metoclopramide should not be taken for longer than 5 days [EMA, 2013].
  • People with asthma, atopic allergy, bradycardia, or cardiac conduction disturbances. 

[EMC, 2024a; BNF, 2024]

Adverse effects

• Metoclopramide is generally well tolerated. However:
• • Extrapyramidal reactions (usually dystonic) can occur. Most reactions occur within 36 hours of starting and disappear within 24 hours of stopping treatment. The incidence of dystonic reactions is more common in young adults under the age of 20 years (especially girls and young women) and the elderly.
  • Raised serum prolactin levels with prolonged treatment can cause galactorrhoea, irregular periods, and gynaecomastia.
  • Neuroleptic malignant syndrome has very rarely been reported with metoclopramide use.
• The maximum duration of therapy with metoclopramide is 5 days [EMA, 2013].
  • Following a review by the European Medicines Agency, metoclopramide should not be prescribed for more than 5 days. The EMA review confirmed the well-known neurological risks such as short-term extrapyramidal adverse effects. This risk is higher in children, although tardive dyskinesia was reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The EMA states that the risks outweighed the benefits of metoclopramide treatment in conditions requiring long-term treatment. There have also been very rare cases of serious cardiovascular adverse effects, particularly after injection.

[EMC, 2024a; BNF, 2024]

Drug interactions

Key drug interactions include:

• Levodopa or dopaminergic agonists — avoid in combination with metoclopramide due to mutual antagonism.
• Anticholinergics and morphine derivatives — may have both a mutual antagonism with metoclopramide on digestive tract motility.
• CNS depressants — sedative effects are potentiated.
• Neuroleptics — additive effect with other neuroleptics on the risk of extrapyramidal disorders.
• Serotonergenics — use of metoclopramide with serotonergic drugs such as SSRIs may increase the risk of serotonin syndrome.
• Digoxin — metoclopramide may decrease digoxin bioavailability. Careful monitoring of digoxin plasma concentration is required.
• Cyclosporine — metoclopramide increases cyclosporine bioavailability. Careful monitoring of cyclosporine plasma concentration is required.
• Strong CYP2D6 inhibitors — metoclopramide levels are increased when co-administered with strong CYP2D6 inhibitors such as fluoxetine and paroxetine. People should therefore be monitored for adverse reactions.

[EMC, 2024a; BNF, 2024]

Pregnancy and breastfeeding

Pregnancy

• Published fetal exposure data are limited, but there is no evidence of an increase in congenital malformations in exposed pregnancies, but a possible higher incidence of premature delivery in one small cohort study [UKTIS, 2019a]. Avoid at the end of pregnancy due to the potential for extrapyramidal syndrome in the newborn.

Breastfeeding 

• Most manufacturers recommend avoiding. The NHS Specialist Pharmacy Service states that metoclopramide can be used with caution during breastfeeding for short-term (maximum 5 days), low-dose use (dose not exceeding 30 mg a day) but monitoring is required. It should be avoided in people with depression. See the NHS Specialist Pharmacy Service website for more information.

[EMC, 2024a; BNF, 2024]

• Cyclizine should be used with caution in people with:
  • Liver dysfunction — cyclizine can be used in people whose metabolic and synthetic function is unaffected (such as in mild hepatitis). However, seek specialist advice before using cyclizine in people with moderate hepatic impairment. It must be avoided in people with severe hepatic impairment, such as those with cirrhosis or encephalopathy who may decompensate, because of its sedative effects.
  • Urinary retention, prostatic hypertrophy, angle-closure glaucoma, or pyloroduodenal obstruction — if possible, avoid using sedating antihistamines such as cyclizine because of their significant antimuscarinic activity (particularly in elderly people).
  • Epilepsy — avoid cyclizine if possible, as it can reduce the seizure threshold.
  • Severe heart failure — avoid using cyclizine if possible, as it may decrease cardiac output.

[EMC, 2024b; BNF, 2024]

Adverse effects

• The most commonly reported adverse effects are nervous system disorders including agitation, angle closure glaucoma, and depression:
• • Elderly people are particularly susceptible (and so lower doses are recommended).
  • Sedating antihistamines may cause drowsiness.
  • Anticholinergic adverse effects may also occur, for example, blurred vision and dry mouth.

[EMC, 2024b; BNF, 2024]

Drug interactions

Key drug interactions include:

• CNS depressants — additive effects may occur.
• Anticholinergics/antimuscarinics (including atropine, TCAs and MAOIs) — additive effects may occur.

[EMC, 2024b; BNF, 2024]

Pregnancy and breastfeeding

Pregnancy 

• The published data on the safety of cyclizine are limited, but there is no robust evidence of an increased risk of infant congenital malformation [UKTIS, 2019a]. The manufacturer recommends avoiding use during pregnancy.

Breastfeeding 

• Most manufacturers recommend avoiding. The NHS Specialist Pharmacy Service states that cyclizine, for short-term use, can be used with caution during breastfeeding, but monitoring is required. Repeated use may pose a risk of infant sedation. See the NHS Specialist Pharmacy Service website for more information.

[EMC, 2024b; BNF, 2024]

Contraindications and cautions

• Chlorphenamine should be avoided in people who:
• • Have been treated with monoamine oxidase inhibitors (MAOIs) in the last 2 weeks — intensified anticholinergic effects.
• Sedating antihistamines should be used with caution in people with:
  • Liver dysfunction — chlorphenamine can be used in people whose metabolic and synthetic function is unaffected (such as in mild hepatitis). However, seek specialist advice before using chlorphenamine in people with more severe hepatic impairment.
  • Urinary retention, prostatic hypertrophy, angle-closure glaucoma, or pyloroduodenal obstruction — if possible, avoid using sedating antihistamines because of their significant antimuscarinic activity (particularly in elderly people).
  • Epilepsy — avoid chlorphenamine if possible, as it may reduce the seizure threshold.

[EMC, 2023d; BNF, 2024]

Adverse effects

The most commonly reported adverse effects are nervous system disorders:

• Children and elderly people are more susceptible to adverse effects (consideration of a lower daily dose is recommended).
• Chlorphenamine may cause drowsiness, disturbance in concentration, dizziness, and headache.
• Anticholinergic adverse effects may also occur, for example, blurred vision and dry mouth.

[EMC, 2023d; BNF, 2024]

Drug interactions

Key drug interactions with chlorphenamine include:

• Hypnotics and anxiolytics — increased sedative effects.
• Phenytoin — chlorphenamine inhibits phenytoin metabolism and can lead to phenytoin toxicity.
• Monoamine oxidase inhibitors (MAOIs) —the anticholinergic effects of chlorphenamine are intensified by MAOIs. Do not prescribe chlorphenamine to a person who has been treated with MAOIs within the last 14 days.

[EMC, 2023d; BNF, 2024]

Pregnancy and breastfeeding

Pregnancy 

• There is currently no evidence of an increased risk of fetal toxicity following chlorphenamine use in pregnancy [UKTIS, 2019b], however, most manufacturers advise avoiding use during pregnancy. Use in late pregnancy may cause adverse effects in neonates such as irritability, paradoxical excitability and tremor.

Breastfeeding

• The Specialist Pharmacy Service states that there is extensive experience of the safe use of chlorphenamine in breastfeeding. However, the Summary of Product Characteristics for chlorphenamine states that it should not be used in breastfeeding unless considered medically essential.

[EMC, 2023d; BNF, 2024]