Cetirizine Safety Alert May 2025
The FDA has issued a drug safety communication warning that discontinuing Zyrtec (cetirizine) after long-term use may result in rare but severe pruritus within a few days, which may sometimes require medical intervention. Symptoms generally resolve in most patients who restart cetirizine and in some who taper off after restarting. The FDA is revising the prescribing information for both prescription and OTC formulations to include a new warning about pruritus.
Therapeutic Category
- Antihistamine
Dosing:
Allergic rhinitis, perennial:
Infants 6 to <12 months: Oral: 2.5 mg once daily.
Children 12 to 23 months: Oral: Initial: 2.5 mg once daily; dosage may be increased to 2.5 mg twice daily.
Allergic symptoms, hay fever:
Children 2 to 5 years: Oral: Initial: 2.5 mg once daily; dosage may be increased to 2.5 mg twice daily or 5 mg once daily; maximum daily dose: 5 mg/day.
Children ≥6 years and Adolescents: Oral: 5 to 10 mg once daily.
Anaphylaxis, adjunctive therapy: Limited data available: Note: Do not use for initial or sole treatment of anaphylaxis; H1 antihistamines are not effective for upper or lower airway obstruction or shock. If cutaneous symptoms persist, dose may be repeated in 24 hours (see Urticaria, acute dosing).
Infants ≥6 months and Children <2 years: Oral: 2.5 mg once.
Children 2 to 5 years: Oral 2.5 to 5 mg once.
Children >5 years and Adolescents: Oral: 5 to 10 mg once.
Urticaria, acute:
IV: Infants ≥6 months to Children ≤5 years: 2.5 mg every 24 hours.
Children 6 to 11 years: 5 mg or 10 mg every 24 hours; reserve higher dose for more severe symptoms.
Children ≥12 years and Adolescents: 10 mg every 24 hours.
Oral:
Infants ≥6 months and Children <2 years: Oral: 2.5 mg once daily.
Children 2 to 5 years: Oral: 2.5 to 5 mg once daily.
Children >5 years and Adolescents: Oral: 5 to 10 mg once daily.
Urticaria, chronic spontaneous:
Note: Considered first-line therapy for management of chronic urticaria; if response inadequate after 2 to 4 weeks of therapy or symptoms intolerable, consider increasing the dose of cetirizine (as age and weight permits) as second-line treatment rather than changing therapy.
Infants 6 to <12 months: Oral: 2.5 mg once daily.
Infants ≥12 months and Children <2 years: Oral: Initial: 2.5 mg once daily; dosage may be increased to 2.5 mg twice daily.
Children 2 to 5 years: Oral: Initial: 2.5 mg once daily; dosage may be increased to 2.5 mg twice daily or 5 mg once daily; maximum daily dose: 5 mg/day.
Children 6 to 11 years: Oral: 5 mg once daily or twice daily.
Children ≥12 years and Adolescents: Oral: 10 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing: Kidney Impairment:
IV: Note: Has only been evaluated for acute indications (short-term therapy).
Infants ≥6 months and Children <6 years: Avoid use in patients with any degree of renal impairment; has not been studied.
Children ≥6 years and Adolescents: Moderate to severe impairment; end-stage renal disease on dialysis: No adjustment necessary; monitor for antihistamine side effects and adjust therapy if needed.
Oral: There are no dosage adjustments provided in the manufacturer’s labeling; however, the following adjustments have been recommended:
Infants, Children, and Adolescents:
GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 29 mL/minute/1.73 m2: Decrease dose by 50%.
GFR <10 mL/minute/1.73 m2: Not recommended.
Intermittent hemodialysis or peritoneal dialysis: Decrease dose by 50%.
Dosing: Liver Impairment:
IV: Note: Has only been evaluated for acute indications (short-term therapy).
Infants ≥6 months to Children <6 years: Avoid use with hepatic impairment; has not been studied.
Children ≥6 years and Adolescents: No dosage adjustment required; monitor for antihistamine side effects and adjust therapy if needed.
Oral: Infants ≥6 months, Children, and Adolescents: There are no dosage adjustments provided in manufacturer’s labeling.
Adverse Reactions (Significant): Considerations
CNS effects
Cetirizine may cause CNS depression, including sedated state, drowsiness, and fatigue. There are rare reports of psychosis and delusion. In overdose in children, sedation is more likely to occur than with other second-generation antihistamines.
Mechanism: Dose-related; low brain uptake, binding to ~30% of H1 cerebral receptors.
Onset: May occur after 1 or 2 doses. Onset of psychosis has occurred 2 to 7 days after initiation of cetirizine.
More sedating than other second-generation antihistamines, including loratadine and fexofenadine, but less sedating than first-generation antihistamines such as diphenhydramine
Adverse Reactions
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Nervous system: Drowsiness (2% to 4%), headache (14%)
1% to 10%:
Cardiovascular: Cardiac failure (<2%), chest pain (<2%), edema (<2%), facial edema (<2%), flushing (<2%), hypertension (<2%), lower extremity edema (<2%), palpitations (<2%), peripheral edema (<2%), syncope (<2%), tachycardia (<2%)
Dermatologic: Acne vulgaris (<2%), alopecia (<2%), bullous rash (<2%), cutaneous nodule (<2%), dermatitis (<2%), diaphoresis (<2%), eczema (<2%), erythematous rash (<2%), furunculosis (<2%), hyperkeratosis (<2%), hypertrichosis (<2%), maculopapular rash (<2%), pallor (<2%), pruritus (<2%), seborrhea (<2%), skin photosensitivity (<2%), skin rash (<2%), urticaria (<2%), xeroderma (<2%)
Endocrine & metabolic: Decreased libido (<2%), dehydration (<2%), diabetes mellitus (<2%), heavy menstrual bleeding (<2%), hot flash (<2%), increased thirst (<2%), intermenstrual bleeding (<2%), weight gain (<2%)
Gastrointestinal: Abdominal pain (children: 4% to 6%), ageusia (<2%), anorexia (<2%), aphthous stomatitis (<2%), constipation (<2%), dental caries (<2%), diarrhea (children: 2% to 3%), dysgeusia (<2%), dyspepsia (<2%), enlargement of abdomen (<2%), eructation (<2%), flatulence (<2%), gastritis (<2%), hemorrhoids (<2%), increased appetite (<2%), melena (<2%), nausea (children: 3%), sialorrhea (<2%), stomatitis (<2%), tongue discoloration (<2%), vomiting (children: 2% to 3%), xerostomia (adolescents and adults: 5%)
Genitourinary: Cystitis (<2%), dysmenorrhea (<2%), dysuria (<2%), hematuria (<2%), leukorrhea (<2%), mastalgia (<2%), urinary frequency (<2%), urinary incontinence (<2%), urinary retention (<2%), urinary tract infection (<2%), vaginitis (<2%)
Hematologic & oncologic: Hemophthalmos (<2%), lymphadenopathy (<2%), purpuric disease (<2%), rectal hemorrhage (<2%)
Hepatic: Hepatic insufficiency (<2%)
Hypersensitivity: Angioedema (<2%), tongue edema (<2%)
Nervous system: Abnormality in thinking (<2%), agitation (<2%), altered sense of smell (<2%), amnesia (<2%), anxiety (<2%), ataxia (<2%), confusion (<2%), depersonalization (<2%), depression (<2%), dizziness (adolescents and adults: 2%), emotional lability (<2%), euphoria (<2%), fatigue (4% to 6%), hyperesthesia (<2%), hypertonia (<2%), hypoesthesia (<2%), impaired concentration (<2%), insomnia (≤9%), malaise (≤4%), migraine (<2%), myasthenia (<2%), nervousness (<2%), nightmares (<2%), pain (<2%), paralysis (<2%), paresthesia (<2%), rigors (<2%), sleep disorder (<2%), twitching (<2%), vertigo (<2%), voice disorder (<2%)
Neuromuscular & skeletal: Arthralgia (<2%), arthritis (<2%), asthenia (<2%), back pain (<2%), hyperkinetic muscle activity (<2%), lower limb cramp (<2%), myalgia (<2%), myelitis (<2%), osteoarthrosis (<2%), tremor (<2%)
Ophthalmic: Accommodation disturbance (<2%), blepharoptosis (<2%), blindness (<2%), conjunctivitis (<2%), eye pain (<2%), glaucoma (<2%), periorbital edema (<2%), visual field defect (<2%), xerophthalmia (<2%)
Otic: Deafness (<2%), otalgia (<2%), ototoxicity (<2%), tinnitus (<2%)
Renal: Polyuria (<2%)
Respiratory: Bronchitis (<2%), bronchospasm (children: 3%), dyspnea (<2%), epistaxis (children: 4%), hyperventilation (<2%), increased bronchial secretions (<2%), nasal polyposis (<2%), pharyngitis (2% to 6%), pneumonia (<2%), respiratory system disorder (<2%), rhinitis (<2%), sinusitis (<2%), upper respiratory tract infection (<2%)
Miscellaneous: Fever (<2%)
<1%:
Cardiovascular: Presyncope
Dermatologic: Hyperhidrosis
Nervous system: Feeling hot
Frequency not defined:
Hepatic: Increased serum transaminases (transient, reversible)
Nervous system: Irritability
Miscellaneous: Fussiness in an infant or toddler
Postmarketing:
Cardiovascular: Severe hypotension
Gastrointestinal: Cholestasis
Hematologic & oncologic: Hemolytic anemia, thrombocytopenia
Hepatic: Hepatitis, increased serum bilirubin
Hypersensitivity: Anaphylaxis
Nervous system: Aggressive behavior, delusion, hallucination, psychosis, sedated state, seizure, suicidal ideation, suicidal tendencies
Neuromuscular & skeletal: Orofacial dyskinesia
Renal: Glomerulonephritis
Contraindications
Hypersensitivity to cetirizine, hydroxyzine, levocetirizine, or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to piperazine derivatives; severe renal impairment (CrCl <10 mL/minute).
Warnings/Precautions
Concerns related to adverse effects:
• Pruritus: Rebound pruritus has been reported within several days after stopping cetirizine, usually after long-term (eg, months to years) use.
Disease-related concerns:
• Hepatic impairment: Use with caution; consider dosage adjustment.
• Renal impairment: Use with caution; consider dosage adjustment.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Warnings:
Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; the AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported. Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. The FDA does not recommend OTC uses for these products in pediatric patients <2 years of age and recommends using with caution in pediatric patients ≥2 years of age. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution.
Administration:
Oral: Administer without regard to food.
Chewable tablet: Chew tablet before swallowing; may be taken with or without water.
Dissolving tablet: Allow tablet to melt in mouth; may be taken with or without water.
Liquid: Administer with an accurate measuring device; do not use a household teaspoon (overdosage may occur).
Parenteral: IV: Administer IV undiluted over 1 to 2 minutes; do not administer IM or SubQ.
Storage/Stability
Capsule, tablet, oral solution, injection: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Injection: Discard unused portion.
Use
Prescription products:
Oral syrup: Relief of symptoms associated with perennial allergic rhinitis (FDA approved in ages 6 to 23 months); treatment of the uncomplicated skin manifestations of chronic spontaneous urticaria (FDA approved in ages 6 months to 5 years).
Parenteral: Treatment of acute urticaria (FDA approved in ages ≥6 months and adults).
OTC products: Relief of symptoms of hay fever or other respiratory allergies, relief of symptoms of common cold (OTC products: Oral syrup: FDA approved in ages ≥2 years and adults; tablets: FDA approved in ages ≥6 years and adults).
Has also been used as adjunct therapy in management of cutaneous symptoms of anaphylaxis.
Food Interactions
Cetirizine’s absorption and maximal concentration are reduced when taken with food. Management: May be taken without regard to meals.
Mechanism of Action
Competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract