Centre of Evidence of Dermatology Best practice guidelines

Guidelines chronic spontaneous urticaria Updated on december 2019


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Treatment with second-generation anti-H1 antihistamines
in adults

Back to decision-making tree Print last updated on 18/09/2020

Conventional dosage (single dose per day)

Second-generation anti-H1 antihistamines at conventional dose (single dose, MA-compliant) are effective and well tolerated.

They are therefore the first-line treatment in CSU.

There are few reasons to prefer one molecule over another.

Experts recommend taking this medication in the evening, because of the risk of drowsiness and to avoid night-time flare-ups.

Multiple doses

Increasing the dose by a factor of 4 has shown good results with cetirizine and levocetirizine, providing better symptom control than the conventional dose.

The dose increase should be rapid (< 2 months) as efficacy is demonstrated in the short term: the time before increasing the dose depends on the study, ranging from 1 week to 2 months. The manner in which the dose is increased is not uniform across studies, where it is most often increased incrementally.

Most experts, in case of resistance to conventional doses of anti-H1 antihistamines, use a quadruple dose of anti-H1 antihistamines right away, then decrease to 3 doses, then 2 or even 1 after achieving remission at the minimum effective dose.

Cardiovascular risk

An increased risk of QT prolongation and torsades de pointes is documented with hydroxyzine, mequitazine and promethazine for first-generation anti-H1 antihistamines and with mizolastine, ebastine and bilastine for second-generation anti-H1 antihistamines. This risk is dose-dependent.

→see appendix 8 in documentation tab

Interactions with other drugs

anti-H1 drugs for which the risk of QT prolongation is documented (mizolastine, ebastine, bilastine, hydroxyzine, mequitazine and promethazine) should not be combined with drugs known to prolong QT (certain neuroleptics, antiarrhythmics, antidepressants, antimalarials, antibiotics, antifungals, methadone, etc; consult the regional pharmacovigilance centre) nor with powerful enzyme-inhibiting drugs (such as certain macrolides, azole antifungals, anti-HIV, etc; consult the regional pharmacovigilance centre), which increase their concentration and increase the risk of rhythm disorders.

Risks in elderly patients

Because of their specific pharmacokinetics (especially their elimination), the dosage of some anti-H1 drugs should be reduced in patients with impaired renal or hepatic function and in the elderly.

anti-H1 antihistamines and pregnancy

In the first trimester, a second-generation anti-H1 antihistamine that has a considerable history of use during pregnancy is to be preferred (cetirizine, levocetirizine or desloratadine as first-line treatment, and fexofenadine as second-line treatment). After the first trimester, all non-sedating and minimally atropinic (second-generation) anti-H1 antihistamines can be used.

If a first-generation anti-H1 antihistamine is desired in the first trimester, chlorphenamine, dexchlorpheniramine, pheniramine or promethazine may be prescribed, but their use is not recommended at the end of pregnancy because of the risk of sedation and neonatal atropinic adverse effects (tachycardia, abdominal distension, meconium ileus, etc.).

anti-H1 antihistamines and breastfeeding

anti-H1 antihistamines pass into breast milk to varying degrees. Most are not recommended during breastfeeding because of the risk of sedation. However, breastfeeding is possible with cetirizine, levocetirizine, loratadine and desloratadine, as the data available to date indicate low breastmilk uptake. It is not recommended to discontinue these anti-H1 antihistamines during breastfeeding. The objective is to achieve the minimum effective dose.

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treatment with anti-H2 antihistamines

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