Cetirizine hydrochloride

What it is

Cetirizine is a second-generation oral antihistamine and the main active metabolite of hydroxyzine. It is sold over the counter as 5 mg and 10 mg tablets, chewables, orally disintegrating tablets and syrup, and by prescription as a syrup for young children. It blocks histamine H1 receptors, mostly outside the brain, although it crosses into the brain more than some of its class and is measurably sedating.

What the research says

For allergic rhinitis, network meta-analysis of randomised trials shows oral antihistamines as a class beat placebo on symptom scores, with cetirizine among the more effective agents but not the top-ranked one. For chronic spontaneous urticaria, a Cochrane review found cetirizine 10 mg daily produced complete suppression of hives in more people than placebo (RR 2.72, 95% CI 1.51 to 4.91), while rating the evidence low quality. For eczema, Cochrane found cetirizine no better than placebo. It is sedating in a dose-related way, and a documented and now formally warned-about problem is severe rebound itching after stopping long-term daily use.

Evidence grade: Well established.

How it works

Drug class: Second-generation (peripherally selective) H1-receptor antagonist; a piperazine and the carboxylated metabolite of hydroxyzine

Histamine released by allergic cells docks onto H1 receptors in the nose, eyes and skin and produces itching, sneezing, running nose and hives. Cetirizine sits on those receptors and blocks histamine from acting there, mainly in the body rather than the brain, which is why it causes less drowsiness than older antihistamines but is not drowsiness-free. (Source 1)

What it is used for

• A network meta-analysis of 18 randomised trials in 9,419 people found every oral antihistamine studied, cetirizine included, beat placebo on total and individual symptom scores; rupatadine ranked highest and loratadine lowest. Evidence: established. (Source 2)
• Cochrane found cetirizine 10 mg once daily produced complete suppression of urticaria in more people than placebo (RR 2.72, 95% CI 1.51 to 4.91) in the short and intermediate term, but graded the evidence low quality because estimates came from few and small studies. Evidence: limited. (Source 3)
• A 2019 Cochrane review found cetirizine was no better than placebo for physician-assessed signs or patient-assessed symptoms, in a 795-child 18-month trial (moderate quality) and an 84-adult 4-week trial (low quality). Evidence: not-supported. (Source 4)

Interactions

• Alcohol and other CNS depressants (label): Combining cetirizine with alcohol or other sedating drugs reduces alertness and impairs mental performance more than either alone. (Source 5)
• Theophylline (pharmacokinetic study): Theophylline slows the clearance of cetirizine slightly, so blood levels of cetirizine run a little higher. (Source 6)

Stopping it

• This is the interaction between cetirizine and time that most people do not expect. A US FDA case-series analysis found 146 reports of intense itching starting a median of 2 days after stopping cetirizine, after a median of 24 months of use, and it came back in 54 of the 55 people who stopped a second time. The authors describe this as evidence of an association from a case series, not as proof of cause, and say the mechanism by which it happens is unknown. (Source 7)
• The mechanism is not understood. Searching the same adverse-event database for other second-generation antihistamines did not turn up enough to call it a class effect, although five comparable cases were found for levocetirizine, the R-enantiomer of cetirizine. One suggested explanation is that heavily occupied H1 receptors produce itch when a short half-life drug clears. (Source 8)
• The FDA acted on this evidence on 16 May 2025 and required the warning to be added to the labels of cetirizine and levocetirizine products. That is a regulatory position built on spontaneous reports, not on a randomised discontinuation trial, and no trial of tapering versus stopping abruptly exists in what we searched. (Source 9)

What goes wrong

Stopping cetirizine after months to years of daily use can trigger intense rebound itching that recurs on every attempt to stop. (Source 10)

• Case series, Low certainty.
• Size: 146 cases in the FDA Adverse Event Reporting System and published literature through 24 April 2017.
• Who: median age 38 years (range 6 to 71), predominantly female (110 of 146)
• How long: median duration of cetirizine use before stopping 24 months (range 0.3 to 172.2 months)
• Result: median time to onset of itching after stopping 2 days (range 0.5 to 5 days); of 55 cases who stopped again after restarting, 54 had the itching return. Spontaneous reporting cannot give a rate, only an association.
• Funding: US Food and Drug Administration staff analysis (independent of manufacturer)

We identified 146 cases of pruritus after discontinuation of cetirizine.

Cetirizine causes dose-related drowsiness above placebo rates. (Source 11)

• Official position, Low certainty.
• Size: pooled paediatric trial data as summarised in the label.
• Who: children aged 6 to 11 in placebo-controlled trials.
• How long: not stated on the label.
• Result: somnolence 1.3% on placebo, 1.9% at 5 mg, 4.2% at 10 mg. This is the manufacturer's pooled tabulation in an FDA label, not an independent meta-analysis.
• Funding: manufacturer data reproduced in the approved label.

somnolence appeared to be dose-related, 1.3% in placebo, 1.9% at 5 mg and 4.2% at 10 mg.

The FDA's position since 16 May 2025 is that a warning about severe itching after stopping long-term cetirizine or levocetirizine is required. (Source 9)

• Official position, Certainty not rated.
• Size: not stated in the communication text we read.
• Who: people who used the medicines daily for long periods, mostly longer than three months.
• How long: communication dated 05-16-2025.
• Result: a regulatory labelling requirement, not an effect size.
• Funding: not applicable.

The U.S. Food and Drug Administration (FDA) is warning that patients stopping the oral allergy medicines cetirizine (Zyrtec) or levocetirizine (Xyzal) after long-term use may experience rare but severe itching.

What the evidence supports

Oral antihistamines including cetirizine reduce allergic rhinitis symptom scores more than placebo. (Source 2)

• Meta-analysis, Moderate certainty.
• Size: 9,419 participants across 18 randomised controlled studies.
• Who: patients with allergic rhinitis.
• How long: not stated in the abstract; typical trials ran 2 to 4 weeks.
• Result: all treatments beat placebo on total symptom score. Ranked by SUCRA, rupatadine 20 mg and 10 mg were highest for total symptom score (99.7%, 76.3%); levocetirizine 5 mg ranked high for nasal itching and sneezing; loratadine 10 mg ranked lowest above placebo. Separate cetirizine effect sizes with CIs were not reported in the abstract.
• Funding: not stated.

All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction.

Cetirizine 10 mg daily completely suppressed chronic spontaneous urticaria in more people than placebo. (Source 3)

• Systematic review, Low certainty.
• Size: 73 studies with 9,759 participants in the whole review; the cetirizine comparison rests on few studies.
• Who: people with chronic spontaneous urticaria.
• How long: short term (up to 2 weeks) and intermediate term (over 2 weeks up to 3 months)
• Result: complete suppression of urticaria RR 2.72, 95% CI 1.51 to 4.91. The review's own words: quality of the evidence was low, downgraded for imprecision.
• Funding: not stated.

Cetirizine 10 mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91).

What the evidence does not support

Cetirizine added to topical treatment was no better than placebo for eczema. (Source 4)

• Systematic review, Low certainty.
• Size: 795 children over 18 months in one trial; 84 adults over 4 weeks in another.
• Who: people with eczema already using topical treatment.
• How long: 18 months and 4 weeks respectively.
• Result: in adults, no evidence of differences in patient-assessed symptoms, adverse events (RR 1.11, 95% CI 0.50 to 2.45) or physician-assessed signs; in children, SCORAD fell in both groups with a non-significant between-group difference. Evidence graded moderate quality for the child trial and low for the adult trial.
• Funding: not stated.

Cetirizine was no better than placebo in terms of physician‐assessed clinical signs nor patient‐assessed symptoms, and we found no evidence that loratadine was more beneficial than placebo, although all interventions seem safe.

Where the evidence is mixed

The same Cochrane review rates its own evidence as low quality and says no antihistamine stands out. (Source 12)

• Systematic review, Low certainty.
• Size: 73 studies, 9,759 participants.
• Who: people with chronic spontaneous urticaria.
• How long: short and intermediate term.
• Result: no numerical effect; a certainty judgement. Withdrawals for adverse events did not differ between active and placebo groups, and quality-of-life evidence was insufficient.
• Funding: not stated.

The quality of the evidence was affected by the small number of studies in each comparison and the small sample size for many of the outcomes, prompting us to downgrade the quality of evidence for imprecision (unless stated for each comparison, the quality of the evidence was low). No single H1‐antihistamine stands out as most effective.

Where the research disagrees

How good the evidence for antihistamines in chronic urticaria actually is

• Sharma and colleagues, Cochrane 2014 (results), systematic review of randomised trials: Cetirizine 10 mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). (Source 3)
• The same review, on its own certainty, GRADE certainty assessment within the same systematic review: Although the results of our review indicate that at standard doses of treatment, several antihistamines are effective when compared with placebo, all results were gathered from a few studies or, in some cases, from single‐study estimates. (Source 12)

How much

• Reference intake: There is no reader dose here. For the over-the-counter product the FDA label's position for adults and children 6 and over is one 10 mg tablet once daily, with a 5 mg product possibly appropriate for less severe symptoms; prescription paediatric dosing is set by the prescriber. (Source 13)
• Upper limit: The over-the-counter label's stated maximum is one 10 mg tablet in 24 hours. (Source 13)
• Studied: Cochrane's urticaria review found cetirizine 10 mg once daily effective for complete suppression in the short and intermediate term. (Source 12)
• Studied: Eczema trials gave cetirizine 0.5 mg/kg/day to 795 children for 18 months and 10 mg/day to 84 adults for four weeks. (Source 14)

A common belief, and what the research shows

The belief: Cetirizine is a completely non-drowsy antihistamine you can take daily forever and stop whenever you like.

What the research shows: Neither half holds. Drowsiness is dose-related and above placebo in the manufacturer's own pooled data: "somnolence appeared to be dose-related, 1.3% in placebo, 1.9% at 5 mg and 4.2% at 10 mg." And stopping after long daily use is a recognised problem: "We identified 146 cases of pruritus after discontinuation of cetirizine." The FDA now requires a warning about it.

Questions and answers

What is it?

Cetirizine is an antihistamine tablet, syrup or dissolving tablet, sold mostly over the counter. Chemically it is the main active breakdown product of the older antihistamine hydroxyzine. It is classed as second-generation because it acts mainly on histamine receptors outside the brain. (Source 1)

What does it do in the body?

During an allergic reaction, cells release histamine, which acts on H1 receptors to produce itching, sneezing, a running nose, watery eyes and hives. Cetirizine occupies those receptors so histamine cannot. Because it targets receptors mainly outside the brain, it sedates less than older antihistamines, but it still reaches the brain enough to cause measurable drowsiness in some people. (Source 1)

Is it good or bad for you?

Good for what it was tested for, unimpressive elsewhere, and with a real tail risk. It beats placebo for allergic rhinitis symptoms and for suppressing chronic hives, though Cochrane rates that evidence low quality and says no one antihistamine stands out. It does not help eczema. Long-term daily use carries a documented rebound-itching problem on stopping. (Source 12)

How do you get more of it?

This question does not apply in the way it does for a nutrient. Cetirizine is a manufactured medicine, not something the body makes or that food supplies; the only source is the drug product itself, over the counter or on prescription. (Source 1)

We searched: We searched the FDA labels, Cochrane reviews and antihistamine meta-analyses; none describes any dietary or endogenous source of cetirizine, because there is none.

If it is harmful, what reduces it?

Cetirizine clears from the body within about a day of the last dose. The complication is that in people who have taken it daily for months or years, stopping is itself what causes the problem: a case series provided evidence of an association between stopping cetirizine and intense itching, starting a median of two days after stopping and returning in 54 of 55 people who tried stopping a second time. The authors say the mechanism is unknown, and no tapering trial exists. (Source 7)

Why might someone be low in it or missing it?

Not applicable: nobody is deficient in cetirizine. What varies is exposure, because it is an over-the-counter product people start and stop on their own; the FDA's 2025 communication was prompted precisely by long, unsupervised daily use. (Source 9)

We searched: We searched the FDA safety communication, the FAERS case series and the drug labels; none frames cetirizine as something a person can be deficient in.

Which whole foods contain it or feed it?

No food contains cetirizine. The only food-related point in the sources we read is that alcohol should be avoided with it, because the combination reduces alertness more than either alone. (Source 5)

We searched: We searched the FDA labels and reviews for food interactions; only alcohol and CNS depressants are addressed.

What happens if you do not have it?

Without it, allergic symptoms and hives run their own course. The measurable consequence in trials is symptom scores: every oral antihistamine tested beat placebo on total and individual allergic rhinitis symptom scores, so not taking one means, on average, worse symptom scores rather than any harm. (Source 2)

How can you test for it?

There is no blood test for cetirizine in routine use and none of the sources we read describes one. What is measured in trials is the outcome rather than the drug: symptom scores for rhinitis, complete suppression of hives for urticaria, SCORAD for eczema. (Source 3)

We searched: We searched Cochrane reviews, the antihistamine network meta-analysis and the FDA labels for any monitoring or blood-level test; only symptom outcome measures appear.

References

1. DailyMed, US National Library of Medicine (FDA-approved labelling; a POSITION, not evidence). CETIRIZINE HYDROCHLORIDE syrup - CLINICAL PHARMACOLOGY / Mechanism of Action. 2010. Read the source
2. Brazilian Journal of Otorhinolaryngology (Elsevier / ScienceDirect). Efficacy of different oral H1 antihistamine treatments on allergic rhinitis: a systematic review and network meta-analysis of randomized controlled trials. 2023. Read the source
3. Cochrane Database of Systematic Reviews (abstract read via Evidence Central / Unbound Medicine). H1-antihistamines for chronic spontaneous urticaria (Main results). 2014. DOI 10.1002/14651858.CD006137.pub2. Read the source
4. Cochrane Database of Systematic Reviews (abstract read via Evidence Central / Unbound Medicine). Oral H1 antihistamines as 'add-on' therapy to topical treatment for eczema (Authors' conclusions). 2019. PMID 30666626, DOI 10.1002/14651858.CD012167.pub2. Read the source
5. DailyMed, US National Library of Medicine (FDA-approved labelling; a POSITION, not evidence). CETIRIZINE HYDROCHLORIDE syrup - PRECAUTIONS (alcohol and CNS depressants). 2010. Read the source
6. DailyMed, US National Library of Medicine (FDA-approved labelling; a POSITION, not evidence). CETIRIZINE HYDROCHLORIDE syrup - Drug Interactions (theophylline). 2010. Read the source
7. Therapeutic Advances in Drug Safety (SAGE). Pruritus after discontinuation of cetirizine (Conclusions). 2019. PMID 31308927, DOI 10.1177/2042098619859996. Read the source
8. Therapeutic Advances in Drug Safety (SAGE). Pruritus after discontinuation of cetirizine (Discussion, mechanism and class-effect search). 2019. PMID 31308927, DOI 10.1177/2042098619859996. Read the source
9. US Food and Drug Administration Drug Safety Communication (a POSITION, dated 05-16-2025). FDA requires warning about rare but severe itching after stopping long-term use of oral allergy medicines cetirizine or levocetirizine (Zyrtec, Xyzal, and other trade names). 2025. Read the source
10. Therapeutic Advances in Drug Safety (SAGE). Pruritus after discontinuation of cetirizine (Results). 2019. PMID 31308927, DOI 10.1177/2042098619859996. Read the source
11. DailyMed, US National Library of Medicine (FDA-approved labelling; a POSITION, not evidence). CETIRIZINE HYDROCHLORIDE syrup - ADVERSE REACTIONS (paediatric somnolence). 2010. Read the source
12. Cochrane Database of Systematic Reviews (abstract read via Evidence Central / Unbound Medicine). H1-antihistamines for chronic spontaneous urticaria (Authors' conclusions). 2014. DOI 10.1002/14651858.CD006137.pub2. Read the source
13. DailyMed, US National Library of Medicine (FDA-approved labelling; a POSITION, not evidence). CETIRIZINE HYDROCHLORIDE - cetirizine hydrochloride tablet - Directions (over-the-counter Drug Facts). 2010. Read the source
14. Cochrane Database of Systematic Reviews (abstract read via Evidence Central / Unbound Medicine). Oral H1 antihistamines as 'add-on' therapy to topical treatment for eczema (Main results, cetirizine comparisons). 2019. PMID 30666626, DOI 10.1002/14651858.CD012167.pub2. Read the source