Previous changes

March 2024 — minor update. A minor typographical error has been corrected. 

January 2024 — minor update. Cetirizine doses for people with renal impairment updated in line with manufacturer's SPC.

June 2023 — minor update. Cetirizine doses for people with renal impairment updated in line with BNF.

November 2022 — minor update. Typographical error corrected. 

September 2022 — reviewed. A literature search was conducted in August 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key controlled trials (RCTs) published since the last revision of the topic. No major changes to recommendations have been made. 

August 2021 — minor update. Recommendations on use of cetirizine in people with renal impairment have been updated in line with the updated manufacturer's Summary of Product Characteristics.

March 2020 — minor update. Topic updated in line with revised SPC on non-sedating antihistamines.

January 2018 — minor update. Adverse effect section of non-sedating antihistamines updated to reflect changes to SPC.

March 2017 — reviewed. A literature search was conducted in March 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key controlled trials (RCTs) published since the last revision of the topic. Changes to the topic include:

• New classification of chronic urticaria: based on the BSACI guideline for the management of chronic urticaria and angioedema published by the British Society for Allergy and Clinical Immunology, chronic urticaria is now classified as (Powell, 2015):
  • Chronic spontaneous urticaria (CSU, previously called chronic idiopathic urticaria).
  • Autoimmune urticaria (in European guidelines this comes under the CSU subtype).
  • Chronic inducible urticaria (previously called physical urticaria).
• Length of treatment course: people with symptoms requiring treatment should be offered a suitable non-sedating antihistamine at the standard licensed dose to be taken daily for up to 4 weeks. Once symptom control has been achieved, antihistamine treatment should be taken daily for 3–6 months (for most people) or as required or prophylactically (for people with infrequent symptoms). 
• Updosing of non-sedating antihistamines: for people not responding to standard doses of antihistamines, the dose of the first choice antihistamine should be increased gradually to up to four times the standard licensed dose (if appropriate). 
• Assessing disease severity and impact on quality of life: this update includes the recommendation to consider assessing disease severity and impact on quality of life using validated tools, such as the Urticaria Activity Score (UAS7) and the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), respectively.

May 2016 — minor update. Text updated to reflect the Medicines and Healthcare products Regulatory Agency (MHRA) safety update on the risk of QT interval prolongation and Torsade de Pointes with hydroxyzine (MHRA, 2015). 

May 2014 — minor update. A link to antihistamine prescriptions has been removed and replaced with a link to a prescribing information section with information on licensed doses of antihistamines.

November 2011 — revised. A literature search was conducted in October 2011 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. The topic has been restructured to improve clarity and navigation. Recommendations on managing people who have had an inadequate response to the standard licensed dose of antihistamine have been changed to include the option to double the standard licensed dose of the first choice antihistamine, before considering referral to secondary care for further management. Issued in January 2012.

March 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made.

May 2008 — minor update. Information included from the British Society for Allergy and Clinical Immunology (BSACI) guidelines for the management of chronic urticaria and angio-oedema (2007). 

February 2008 — minor update. Updated in line with guidelines for the evaluation and management of urticaria in adults and children from the British Association of Dermatologists (BAD, 2007). 

January to April 2007 — this is a new CKS topic, replacing the CKS guidance on Urticaria and angio-oedema. The evidence base has been reviewed in detail, and recommendations are more clearly justified and more transparently linked to the supporting evidence. There are no major changes to the recommendations.

February 2006 — minor update. Black triangle removed from desloratadine. 

November 2005 — minor technical update. 

July 2005 — new CKS patient information leaflet attached.

January 2004 — written. Validated in March 2004 and issued in June 2004.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 August 2022.

HTAs (Health Technology Assessments)

No new HTAs published since 1 August 2022.

Economic appraisals

No new economic appraisals relevant to England since 1 August 2022.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analyses published since 1 August 2022.

Primary evidence

• Giménez-Arnau, A., Ferrucci, S., Ben-Shoshan, M., et al. (2025). Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria: The RILECSU Phase 2 Randomized Clinical Trial. JAMA dermatology. [Abstract]

New policies

No new national policies or guidelines since 1 August 2022.

New safety alerts

No new safety alerts since 1 August 2022.

Changes in product availability

• New product Xolair (omalizumab 75mg, 150mg, 300mg) solution for injection in pre-filled pen. New presentation (already available ad pre-filled syringes) is licensed for the treatment of adults, adolescents and children (≥6 years) with allergic asthma, adults with chronic rhinosinusitis with nasal polyps and adults and adolescents with chronic spontaneous urticaria. See more here.
• New product Allevia Hives (fexofenadine hydrochloride) 180 mg tablets. This non-sedating H1 antihistamine is licensed as a ‘Pharmacy’ medicine for the relief of symptoms associated with chronic idiopathic urticaria in adults and children 12 years and older. See more here.
• New product, omlyclo (omalizumab) 150mg solution for injection pre-filled pen, is licensed for the treatment of chronic sponataneous urticaria. See more here.
• New product: Omlyclo (omalizumab) 300 mg/2 ml Solution is licensed for the treatment of chronic spontaneous urticaria.. See more here.

Basis for recommendation

These recommendations are based on the EAACI/GA²LEN/EDF/WAO Guideline for the definition, classification, diagnosis and management of urticaria [Zuberbier et al, 2018], the management of chronic urticaria in children: a clinical guideline [Caffarelli, 2019], the British Association of Dermatologists Guidelines for the management of people with chronic urticaria [BAD, 2021], and on expert opinion in review articles on urticaria [Marzano, 2015; Kanani, 2018; Hon, 2019; Kayiran, 2019; BMJ Best Practice, 2022a].

History and examination

• Experts advise that the diagnosis of urticaria should be based on a thorough clinical history and examination [Powell, 2015; Marzano, 2015; Kanani, 2018; Hon, 2019; Kayiran, 2019; BMJ Best Practice, 2022a].
• The recommendation to consider assessing the severity of symptoms using a validated tool, such as the Urticaria Activity Score (UAS7), is based on clinical consensus in the EAACI/GA²LEN/EDF/WAO guideline, which highlights that because the signs and symptoms are evaluated by the person with urticaria, the UAS7 is a valuable assessment tool [Zuberbier et al, 2018].
  • The BSACI guideline does not specifically recommend the use of the UAS7 tool, but states that disease-specific quality of life questionnaires/symptom scores are available for determining the frequency, duration, and severity of urticarial episodes [Powell, 2015].
  • Expert opinion in a review article is that the UAS7 tool 'allows for efficient clinical practice, maximizing the information gathered during patient visits while minimizing the use of resources and time' [Moolani, 2016].
    • The Urticaria Severity Score (USS), a 12-question tool, is an alternative tool for monitoring disease severity [Moolani, 2016].
• The information on immunoglobuling E (IgE)-mediated food allergy is based on expert opinion in the BSACI guideline [Powell, 2015].
• The characteristics of an urticarial rash are taken from the EAACI/GA²LEN/EDF/WAO guideline [Zuberbier et al, 2018] and the expert review article  [BMJ Best Practice, 2022a].
• The clinical features of vasculitic urticaria are taken from the EAACI/GA²LEN/EDF/WAO guideline [Zuberbier et al, 2018] and an expert review article on urticaria and angio-oedema [BMJ Best Practice, 2022b].

Investigations not usually required

• Expert opinion in guidelines and review articles is that investigations are not always necessary for the diagnosis of urticaria, but may be needed (especially in people with chronic urticaria) to identify treatable associated conditions/trigger factors and to exclude other unusual conditions, such as urticarial vasculitis[Marzano, 2015; Powell, 2015]  [Kanani, 2018; Hon, 2019; Kayiran, 2019; BMJ Best Practice, 2022a].
• See the section on Investigations for more information.

Basis for recommendation

These recommendations are largely based on The EAACI/GA²LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: [Zuberbier et al, 2018]; the BSACI guideline for the management of chronic urticaria and angioedema published by the British Society for Allergy and Clinical Immunology (BSACI) [Powell, 2015]; the management of chronic urticaria in children: a clinical guideline [Caffarelli, 2019] and on the British Association of Dermatologists Guidelines for the management of people with chronic urticaria [BAD, 2021] and on expert opinion in review articles on urticaria [Marzano, 2015; Powell, 2015; Kanani, 2018; Hon, 2019; Kayiran, 2019; BMJ Best Practice, 2022a]. 

Investigations

• Expert opinion in guidelines and review articles is that:
  • Investigations are not always necessary but may be needed (especially in people with chronic urticaria) to identify treatable associated conditions/trigger factors and to exclude other unusual conditions, such as urticarial vasculitis [Powell, 2015; Marzano, 2015; Zuberbier et al, 2018; BMJ Best Practice, 2022a].
  • The need for investigation to find an underlying cause should be guided by the presentation and response to treatment [Powell, 2015; BAD, 2021].
  • Laboratory tests are not indicated in cases of acute urticaria, unless there are findings on history and physical examination that would indicate the lesions were atypical (for example painful, purpuric, non-blanching, palpable lesions, or lesions that leave residual pigmented skin) [BMJ Best Practice, 2022a].
  • Because acute urticaria will usually resolve spontaneously, laboratory investigations are not usually required, unless supported by the clinical history or physical examination. For people with chronic urticaria, targeted laboratory testing based on clinical suspicion is appropriate [BAD, 2021].
• Based on clinical consensus, the EAACI/GA²LEN/EDF/WAO guideline recommends [Zuberbier et al, 2018]:
  • Limiting routine diagnostic measures to determining the threshold of eliciting factors in inducible urticaria subtypes.
  • Limited extended diagnostic measures in chronic spontaneous urticaria based on the person's history.
  • Very limited routine diagnostic measures in people with chronic spontaneous urticaria.
  • Against any routine diagnostic measures in people with acute urticaria.

Specific investigations

• Thyroid function tests (TFTs)
  • There is evidence that people with urticaria are more likely to have thyroid autoimmunity than people without urticaria.
  • A systematic review and meta-analysis investigated the associations between thyroid autoantibodies and urticaria (n = 14,203 urticaria cases and 12,339 non-urticaria controls) and found that the prevalence of positive thyroid autoantibodies in people with urticaria was higher than for non-urticaria controls [Pan, 2015].
  • A 2022 systematic review and meta-analysis (n = 1,100 urticaria cases and 1,100 matched controls) found the prevalence rates of IgE and IgG autoantibodies in people with chronic spontaneous urticaria are significantly elevated (P < 0.001) and reciprocally correlated [Zhang et al, 2022].
• Allergy testing 
  • The information on the diagnosis of immunological chronic urticaria is based on expert opinion in a systematic clinical review [Lukacs, 2016].
  • Expert opinion in a review article is that skin-prick testing for a broad panel of food or environmental allergens is generally ineffective and is not recommended. However, testing for a specific food or allergen based on the history is more useful and can provide greater diagnostic usefulness [BMJ Best Practice, 2022a].
  • Expert opinion in the BSACI guideline is that the sight of negative skin prick tests will help to reassure the person that allergy is not the cause of their symptoms and may contribute to improved adherence with long-term antihistamine treatment [Powell, 2015].
• Helicobacter pylori screening 
  • There some evidence that prevalence of H. pylori infection is higher in people with urticaria than in people without.
  • Expert opinion in the EAACI/GA²LEN/EDF/WAO guideline is that  specific testing for H. pylori is not indicated on the presence of urticaria alone [Zuberbier et al, 2018]. 
• Elimination of suspected drugs or food
  • The information on when a food allergy can be excluded as a cause of urticaria is based on expert opinion in the BSACI guideline [Powell, 2015].
• Physical challenge
  • The information on the physical challenges is based on expert opinion in the BSACI guideline [Powell, 2015] and the the management of chronic urticaria in children: a clinical guideline [Caffarelli, 2019].

Basis for recommendation

This information is based on expert opinion in review articles on urticaria [Marzano, 2015; Kanani, 2018; Kayiran, 2019] and [BMJ Best Practice, 2022a].

How should I manage a person with urticaria?

For people with urticaria and suspected anaphylaxis (characterized by features of upper or lower airway obstruction or shock), see the CKS topic on Angio-oedema and anaphylaxis for management information.

For people with urticaria and angio-oedema, see the CKS topic on Angio-oedema and anaphylaxis for management information.

For all other people with urticaria:

• Identify and manage the underlying causes/trigger factors of urticaria, where possible. 
  • If avoidable triggers are identified, given clear instructions on avoidance strategies.
    • If the person is taking a drug associated with chronic urticaria, for example a nonsteroidal anti-inflammatory drug (NSAID), it is prudent for the person to have a trial for at least several weeks without this treatment. 
  • If a cause cannot be identified from the history for people with recurrent or persistent urticaria, consider arranging appropriate investigations.
  • Symptom diaries can be useful as an investigative tool to determine the frequency, duration, and severity of the urticarial episodes. Consider assessing the severity of urticaria using a validated tool, such as the Urticaria Activity Score (UAS7).
    • With the UAS7, the person records the severity of itching and the number of weals daily for 7 days. A score of less than 7 in 1 week indicates control of disease, whereas a score of  more than 28 per week indicates severe disease.
• For people with mild urticaria with an identifiable and avoidable cause/trigger, advise that urticaria is likely to be self-limiting without treatment.
• For people with symptoms requiring treatment:
  • Offer a non-sedating antihistamine (for example cetirizine, fexofenadine, or loratadine) for up to 6 weeks (use clinical judgement to determine the duration of treatment).
    • See the section on Prescribing information for detailed information on choice and licensed doses of non-sedating antihistamines.
  • If symptoms are severe, give a short course of an oral corticosteroid (for example prednisolone 40 mg daily for up to 7 days) in addition to the non-sedating oral antihistamine.
    • Consider referral if an oral corticosteroid is indicated in a child younger than 16 years of age. 
    • If rebound symptoms occur, seek specialist advice. Do not repeat the course of oral corticosteroids.
  • If symptoms improve, consider the need for further antihistamine treatment, based on an assessment of the underlying cause, and the duration of symptoms before treatment. 
    • If it is likely that symptoms will be persistent or recurrent (for example in people with chronic spontaneous urticaria), prescribe daily antihistamine treatment for 3–6 months, then review. 
    • If symptoms were short lived and frequent recurrence thought unlikely, prescribe treatment to be taken as required or prophylactically (for example prior to occasions when symptoms would be most unwelcome, such as business meetings). 
  • If there is an inadequate response to the first-line antihistamine treatment, consider the following options, using clinical judgement:
    • In adults, gradually increase the dose of the first-line antihistamine to up to four times the standard licensed dose (off-label use). Consider seeking specialist advice if this approach is being considered in a child.
    • Switch to an alternative non-sedating antihistamine.
    • Consider prescribing a leukotriene receptor antagonist (such as montelukast or zafirlukast) in addition to the non-sedating anti-histamine.
    • Prescribe a topical antipruritic treatment (such as calamine lotion or topical menthol 1% in aqueous cream) to relieve itch.
    • Prescribe an additional sedative antihistamine (such as chlorphenamine) at night, if itch is interfering with sleep. See the section on prescribing information for information on prescribing chlorphenamine.
    • Refer the person to a dermatologist or immunologist.
• Consider assessing the impact of urticaria on the person's quality of life using a validated tool, such as the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL).
  • The CU-Q2oL is a self-administered, 23-item questionnaire on which the person has to indicate, on a Likert scale with multiple options (1: not at all; 5: very much), how much they have been troubled by each problem, with higher scores indicating worse quality of life.
• Arrange referral to:
  • A dermatologist or immunologist for:
    • People with urticaria that is painful and persistent (suspect vasculitic urticaria).
    • People whose symptoms are not well controlled on antihistamine treatment. Secondary care treatment options include cyclosporine, omalizumab, mycophenolate mofetil, or tacrolimus.
    • People with angio-oedema and no wheals that do not respond to first-line treatment.
    • People with acute severe urticaria which is thought to be due to a food or latex allergy.
    • People with forms of chronic inducible urticaria that may be difficult to manage in primary care, for example, solar or cold urticaria.
  • A clinical psychologist for people whose symptoms are adversely affecting their quality of life, for example causing significant social or psychological problems.
• Provide additional information on urticaria. For example:
  • NHS A-Z has useful information on Urticaria (hives).
  • The British Association of Dermatologists (BAD) has produced an information leaflet on Urticaria and Angioedema.
  • Allergy UK, a national charity dedicated to supporting allergy sufferers in the UK, has a useful factsheet on Urticaria (hives) and other skin allergy. It also has a dedicated helpline.

Which non-sedating antihistamine should I prescribe?

• For most adults, cetirizine, loratadine, and fexofenadine are usual choices as their long-term safety has been well established and their once-daily dosage may improve adherence [Powell, 2015; Zuberbier et al, 2018; BAD, 2021]. However, any suitable non-sedating antihistamine can be considered as all are licensed for the treatment of urticaria, and there is no strong evidence that one is more effective than the other 
• [Powell, 2015; Zuberbier et al, 2018; BAD, 2021].
• In children, cetirizine, loratadine, or fexofenadine are usual choices and have been well studied[Zuberbier et al, 2018; Caffarelli, 2019; BAD, 2021]:
  • The choice of antihistamine should depend on the age of the child (licensed ages differ), availabilities (as not all are available in syrup form), and preference (for example what has worked in the past).
  • When considering up-dosing in teenagers, bear in mind that cetrizine may induce somnolence[Sanchez-Borges, 2021b].
  • The British National Formulary for Children (BNFC) states that desloratadine or levocetirizine should be reserved for children who cannot tolerate other treatments, because they do not confer any additional benefit [BNF for children, 2022].
• During pregnancy, oral antihistamines should be avoided where possible, especially during the first trimester. However, if a non-sedating antihistamine is required, loratadine is recommended as there is considerable clinical experience with its use in pregnancy, with no increase in the rate of congenital abnormalities [Powell, 2015]. Cetirizine, desloratadine (an active metabolite of loratadine), or levocetirizine (an isomer of cetirizine) may also be considered [Zuberbier et al, 2018].
  • Most manufacturers of antihistamines advise avoiding their use during pregnancy [BNF, 2022]; however, there is no evidence of teratogenicity with their use.
  • A systematic review and meta-analysis on the risk of adverse pregnancy outcome after first trimester exposure to H1-antihistamines found that they do not appear to be associated with an increased risk of major malformation or other adverse fetal outcomes (spontaneous abortions, prematurity, stillbirth, and low birth weight) [Etwel, 2017].
• During breastfeeding, loratadine and cetirizine are recommended. The lowest effective dose for the shortest period of time should be prescribed [Powell, 2015].
  • Most manufacturers of antihistamines advise avoiding their use during breastfeeding as most antihistamines are present in breast milk (in varying amounts)[Zuberbier et al, 2018; BNF, 2022].
  • However, LactMed (a US drugs and lactation database) states that:
    • Loratadine would not be expected to cause any adverse effects in breastfed infants due to its lack of sedation and low milk levels, but it might have a negative effect on lactation[LactMed, 2018].
    • Cetirizine is probably acceptable during breastfeeding if given in small, occasional doses. However, larger doses or more prolonged use may cause drowsiness and other effects in the infant, or decrease the milk supply particularly before lactation is well established [LactMed, 2021]. 

What are the contraindications and cautions?

• Do not prescribe:
  • Cetirizine to people with:
    • End stage renal disease — estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73 m2.
    • Acute porphyria.

• Prescribe:
  • Cetirizine with caution to people with renal impairment.
    • If the eGFR is 30-59 mL/min/1.73m², use half the normal dose.
    • If the eGFR is 15–29 mL/min/1.73 m2 use 5 mg once every 2 days. 
  • Loratadine with caution to people with hepatic impairment.
    • Reduce dose frequency to alternate days in severe impairment.

[BNF, 2022]

What are the licensed doses for chronic idiopathic urticaria?

• The licensed oral doses of cetirizine are:
  • Children aged 2 years to 5 years — 2.5 mg twice daily.
    • Cetirizine is not licensed for use in children aged under 2 years, but the British National Formulary for Children (BNFC) recommends an unlicensed dose of 250 micrograms/kg twice daily for children aged 1 year [BNF for children, 2022]. 
  • Children aged 6 years to 11 years — 5 mg twice daily.
  • Adults and children aged 12 years and over — 10 mg once daily.
• The licensed oral doses of loratadine are:
  • Children aged 2 years to 11 years and body weight up to 31 kg — 5 mg once a day.
  • Children age 2 years to 11 years and body weight 31 kg and over —10 mg once a day.
  • Adults and children aged 12 years and over — 10 mg once a day.
• The licensed oral dose of fexofenadine is:
  • Adults and children aged 12 years and over — 180 mg once a day.

[BNF, 2022; BNF for children, 2022]

What are the possible adverse effects?

• Non-sedating antihistamines are associated with a lower incidence of drowsiness and sedation (because they penetrate the blood-brain barrier to a lesser extent than sedating antihistamines) [Bernstein, 2014]. However, these adverse effects may still occur.
  • Fexofenadine and loratadine may cause sedation at doses exceeding the recommended doses.
  • Cetirizine may cause sedation at recommended doses.
  • The sedative effects of antihistamines are enhanced when combined with alcohol.   
• Rare adverse effects of antihistamines include hypotension, palpitation, arrhythmias, extrapyramidal effects, dizziness, confusion, depression, sleep disturbances, tremor, convulsions, hypersensitivity reactions (including bronchospasm, angioedema, anaphylaxis, rashes, and photosensitivity reactions), blood disorders, liver dysfunction, nightmares, acute generalised exanthematous pustulosis, arthralgia and angle-closure glaucoma.
• The manufacturer's SPC notes that desloratadine has been associated with an increased incidence of new-onset seizures in patients younger than 20 years of age.

[BNF, 2022; ABPI, 2021a; ABPI, 2021b]

What drug interactions are associated with antihistamines?

• Drug interactions associated with non-sedating antihistamines include:
  • Ritonavir — plasma concentration of non-sedating antihistamines possibly increased by ritonavir. 
  • In addition for fexofenadine:
    • Antacids — absorption of fexofenadine reduced by antacids. 
    • Rifampicin — effects of fexofenadine possibly reduced by rifampicin.
    • Ulipristal acetate — the manufacturer of ulipristal acetate advises that fexofenadine is taken at least 1.5 hours before or after taking ulipristal.
  • In addition for loratadine:
    • Cimetidine — the manufacturer of loratadine advises that plasma concentrations are possibly increased by cimetidine.
    • Erythromycin — the manufacturer of loratadine advises that plasma concentrations are possibly increased by erythromycin.
• Drug interactions associated with all antihistamines include:
  • Alcohol — increased sedative effect when antihistamines are taken with alcohol (possibly less effect with non-sedating antihistamines).
  • Antidepressants (tricyclics, tricyclic-related, and monoamine oxidase inhibitors [MAOIs]):
    • Increased antimuscarinic and sedative effects when antihistamines are taken with tricyclics or MAOIs.
    • Possible increased antimuscarinic and sedative effects when antihistamines are taken with tricyclic-related antidepressants.
  • Antimuscarinics — increased risk of antimuscarinic adverse effects when antihistamines are taken with antimuscarinic drugs (dosage adjustment may be required).
    • Note that many drugs have antimuscarinic effects. Concurrent use of two or more of such drugs can increase the risk of adverse effects, such as dry mouth, urine retention, and constipation. Concurrent use can also lead to confusion in the elderly. Interactions do not generally apply to inhaled antimuscarinics.
  • Anxiolytics, hypnotics, and opioids — increased sedative effect when antihistamines are taken with these groups of drugs.
  • Betahistine — antihistamines theoretically antagonize the effects of betahistine.
  • Midodrine — avoidance of antihistamines advised by manufacturer of midodrine.

 [BNF, 2022] 

Which sedating antihistamine should I prescribe?

• For most adults and children (aged 1 month and older), guidelines now recommend against routinely prescribing sedating anti-histamines [Zuberbier et al, 2018; Caffarelli, 2019; BAD, 2021]:
  • There are concerns about their short and long-term effects on the central nervous system.
  • Only use when there is no alternative available [BAD, 2021].
• During pregnancy, oral antihistamines should be avoided where possible, especially during the first trimester.  
  • Most manufacturers of antihistamines advise avoiding their use during pregnancy; however, there is no evidence of teratogenicity with their use, except for hydroxyzine where toxicity has been reported with high doses in animal studies.
  • The use of sedating antihistamines in the latter part of the third trimester may also cause adverse effects in neonates, such as irritability, paradoxical excitability, and tremor [BNF, 2022].
• During breastfeeding, non-sedating antihistamines are recommended.

What are the contraindications and cautions for chlorphenamine?

• Do not prescribe chlorphenamine to:
  • People with severe hepatic impairment — increased risk of coma.
• Prescribe chlorphenamine with caution in:
  • People with:
    • Hepatic impairment.
    • Epilepsy — avoid antihistamines if possible as they reduce the seizure threshold.
    • Renal impairment.
    • Prostatic hypertrophy.
    • Urinary retention.
    • Severe hypertension or cardiovascular disease.
    • Raised intraocular pressure or glaucoma.
    • Pyloroduodenal obstruction.
    • Asthma, bronchitis, or bronchiectasis.
  • Children and the elderly (as they are more susceptible to adverse effects) — be aware of a reduced maximum daily dose in children and elderly people.

[BNF, 2022]

What are the licensed doses of chlorphenamine for the treatment of chronic idiopathic urticaria?

• Sedating antihistamines are no longer recommended by guidelines for routine use in urticaria.
• The licensed oral daily doses of chlorphenamine are [BNF, 2022; BNF for children, 2022]:
  • Age 2 years to 5 years - 1 mg every 4-6 hours; maximum of 6 mg daily.
    • Chlorphenamine is not licensed for use in children younger than 1 year [ABPI, 2021c], but the British National Formulary for Children (BNFC) recommends an unlicensed dose of 1 mg twice daily for children aged 1 month to 23 months [BNF for children, 2022].
  • Age 6 years to 11 years - 2 mg every 4-6 hours; maximum of 12 mg daily.
  • Age 12 years and over (including adults) — 4 mg every 4-6 hours; maximum of 24 mg daily (12 mg daily in elderly people).
  • If there is an inadequate response to the first-line antihistamine treatment, consider gradually increasing the dose of the first-line antihistamine to up to four times the standard licensed dose in adults (off-label use). Consider seeking specialist advice if this approach is being considered in a child.
• For night time use for urticarial symptoms, consider the following doses (using clinical judgement):
  • Age 1 month to 23 months - 1 mg at night.
  • Age 2 years to 5 years - 2 mg at night.
  • Age 6 years to 11 years - 2 to 4 mg at night.
  • Age 12 years and over (including adults) - 4 mg at night.

What are the possible adverse effects of chlorphenamine?

• Sedating antihistamines (such as chlorphenamine) cause sedation in 10–50% of people, which can persist into the next day [DTB, 2002]. The sedative effects are enhanced when combined with alcohol.   
• Other adverse effects of chlorphenamine include [ABPI, 2021d]:
  • Neurological — dizziness, restlessness, psychomotor impairment, and headaches.
  • Anticholinergic effects — blurred vision, dry mouth, and urinary retention.
  • Skin — urticaria, rash, exfoliative dermatitis, and photosensitivity.
  • Gastrointestinal — nausea, vomiting, abdominal pain, diarrhoea, and dyspepsia.
  • Cardiovascular — palpitations, tachycardia, and arrhythmias.
  • Neuropsychiatric — depressed mood, excitation, irritability, nightmares, and confusion.
• Rare adverse effects of antihistamines include hypotension, extrapyramidal effects, sleep disturbances, tremor, convulsions, hypersensitivity reactions (including bronchospasm, angioedema, and anaphylaxis), blood disorders, liver dysfunction, and angle-closure glaucoma.

[BNF, 2022]

What drug interactions are associated with chlorphenamine?

• Drug interactions associated with chlorphenamine include:
  • Antidepressants (monoamine oxidase inhibitors [MAOIs], tricyclics, and tricyclic-related):
    • Chlorphenamine is contraindicated in people who have been treated with MAOIs within the last fourteen days, due to the increased antimuscarinic and sedative effects when antihistamines are taken with MAOIs [ABPI, 2021d].
    • There is increased antimuscarinic and sedative effects when antihistamines are taken with tricyclics.
    • There is possible increased antimuscarinic and sedative effects when antihistamines are taken with tricyclic-related antidepressants.
  • Phenytoin — chlorphenamine inhibits phenytoin metabolism and can lead to phenytoin toxicity. If symptoms of toxicity are present (confusion, blurred vision, nystagmus, ataxia, or drowsiness), monitor serum phenytoin levels and reduce the dose if necessary.
• Drug interactions associated with all antihistamines include:
  • Alcohol — increased sedative effect when antihistamines are taken with alcohol (possibly less effect with non-sedating antihistamines).
  • Antimuscarinics — increased risk of antimuscarinic adverse effects when antihistamines are taken with antimuscarinic drugs (dosage adjustment may be required).
    • Note that many drugs have antimuscarinic effects. Concurrent use of two or more of such drugs can increase adverse effects, such as dry mouth, urine retention, and constipation. Concurrent use can also lead to confusion in the elderly. Interactions do not generally apply to inhaled antimuscarinics.
  • Anxiolytics, hypnotics, and opioids — increased sedative effect when antihistamines are taken with anxiolytics and hypnotics.
  • Betahistine — antihistamines theoretically antagonize the effects of betahistine.
  • Midodrine — avoidance of antihistamines advised by manufacturer of midodrine.

[BNF, 2022]

What do I need to know about prescribing oral corticosteroids?

• Be aware that:
  • Frequent or prolonged use of systemic corticosteroids is associated with serious adverse effects, including growth retardation in children, diabetes mellitus, high blood pressure, and osteoporosis. However, these are unlikely to be a problem with a single course of prednisolone.
  • It is not necessary to taper the dose when stopping a one-week course of prednisolone.
• For detailed prescribing information on oral corticosteroids, including contraindications and cautions, adverse effects, and drug interactions, see the CKS topic on Corticosteroids - oral.