CLASSES

Second Generation Antihistamines

DEA CLASS

Rx, OTC

DESCRIPTION

Selective low-sedating antihistamine; the drug is the R-enantiomer of cetirizine
Prescription products are used for seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria in adults and pediatric patients 6 months and older
Some non-prescription products are available for use in adults and children as young as 2 years of age

COMMON BRAND NAMES

Xyzal, Xyzal Allergy 24 Hour, Xyzal Children's Allergy 24 Hour, Xyzal Solution

HOW SUPPLIED

Levocetirizine/Xyzal/Xyzal Allergy 24 Hour Oral Tab: 5mg
Levocetirizine/Xyzal/Xyzal Children's Allergy 24 Hour/Xyzal Solution Oral Sol: 2.5mg, 5mL

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

5 mg/day PO.

5 mg/day PO.

5 mg/day PO.

12 years: 5 mg/day PO.
6 to 11 years: 2.5 mg/day PO.
3 to 5 years: 1.25 mg/day PO.
1 to 2 years: 1.25 mg/day PO; up to 0.125 mg/kg/dose PO twice daily has been used off-label for atopic dermatitis.

6 to 11 months: 1.25 mg/day PO.
Less than 6 months: Safety and efficacy have not been established.

DOSING CONSIDERATIONS

No dosage adjustment is needed.

According to the FDA-approved product label, the use of levocetirizine in children less than 12 years of age with any renal impairment is contraindicated. For adult and pediatric patients 12 years and older, the following dosage adjustments are recommended :
CrCl 50 to 80 mL/minute: 2.5 mg PO once daily.
CrCl 30 to 50 mL/minute: 2.5 mg PO once every other day.
CrCl 10 to 30 mL/minute: 2.5 mg PO twice a week; administered every 3 to 4 days.
CrCl less than 10 mL/minute: Use is contraindicated.
 
Hemodialysis
Use of levocetirizine in patients undergoing hemodialysis is contraindicated.

ADMINISTRATION

Administer in the evening.
May administer with or without food.

STORAGE

Xyzal:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Xyzal Allergy 24 Hour:
- Store between 68 to 77 degrees F
Xyzal Children's Allergy 24 Hour:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Xyzal Solution:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Levocetirizine is contraindicated for use in patients with a known hypersensitivity to levocetirizine or to any of the formulation components or who have known cetirizine hypersensitivity. Observed reactions range from urticaria to anaphylaxis. Though not listed in the levocetirizine package labeling, it is recommended to avoid use in patients who have known hydroxyzine hypersensitivity, as cetirizine is a hydroxyzine derivative.

Levocetirizine is contraindicated for use in patients with end stage renal disease/renal failure (CrCl less than 10 mL/minute) and those undergoing dialysis. Levocetirizine is also contraindicated for use in pediatric patients less than 12 years of age with any amount of renal impairment. Dose adjustment is necessary in adolescent and adult patients with mild (CrCl 50 to 80 mL/minute), moderate (CrCl 30 to 50 mL/minute) or severe renal impairment (CrCl 10 to 30 mL/minute). Renal excretion is the primary route of levocetirizine elimination and renal clearance of the drug has been shown to correlate with creatinine clearance.

In clinical trials, somnolence, fatigue, and asthenia have been reported in some patients taking levocetirizine; therefore, patients should be advised to avoid driving or operating machinery or engaging in other hazardous activities until the central nervous system (CNS) effects of the drug are known. Ethanol ingestion or coadministration with other CNS depressants should be avoided when using levocetirizine because additional reductions in alertness and additional impairment of CNS performance may occur.

The safety and efficacy of levocetirizine in neonates and infants less than 6 months of age have not been established.

Available data with levocetirizine use during human pregnancy are insufficient to determine any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of fetal harm with the administration of levocetirizine during organogenesis at doses greatly exceeding the maximum recommended human dose (MRHD) in adults (doses up to 390 and 470 times, respectively, in pregnant rats and rabbits); animal studies are not always indicative of human response.[33350] Self-medication with cetirizine (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and treatment recommendations. The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology consider cetirizine and loratadine as acceptable alternatives in pregnancy, preferably after the first trimester, when first-generation antihistamines are not tolerated.[46717]

There are no data available on the presence of levocetirizine in human milk, the effects on the breastfed infant, or the effects on milk production. Levocetirizine is the R-enantiomer of cetirizine. Cetirizine is excreted in human breast milk, but quantitative amounts are not known.[33350] Because of its lack of sedation and low milk concentrations, loratadine is not expected to cause adverse effects in breastfed babies and loratadine is usually considered compatible with breast-feeding.[27500] The British Society for Allergy and Clinical Immunology also recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women.[37820]

Urinary retention has been reported during post-marketing trials with levocetirizine. Therefore, use levocetirizine with caution in patients with predisposing factors of urinary retention (e.g. bladder obstruction, spinal cord lesion, prostatic hypertrophy). Discontinue levocetirizine if urinary retention occurs.

In the geriatric patient with renal impairment, it is recommended that initial doses of levocetirizine be adjusted. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to the OBRA guidelines, cough, cold, and allergy medications should be used only for a limited duration (less than 14 days) unless there is documented evidence of enduring symptoms that cannot otherwise be alleviated and for which a cause cannot be identified and corrected.

ADVERSE REACTIONS

seizures / Delayed / 0.4-2.0
angioedema / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
hemolytic anemia / Delayed / 0-1.0
suicidal ideation / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
glomerulonephritis / Delayed / Incidence not known
visual impairment / Early / Incidence not known

constipation / Delayed / 7.0-7.0
elevated hepatic enzymes / Delayed / 0-1.0
dyspnea / Early / 0-1.0
dyskinesia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
sinus tachycardia / Rapid / Incidence not known
palpitations / Early / Incidence not known
hypotension / Rapid / Incidence not known
hepatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hallucinations / Early / Incidence not known
dystonic reaction / Delayed / Incidence not known
depression / Delayed / Incidence not known
myoclonia / Delayed / Incidence not known
dysuria / Early / Incidence not known
urinary retention / Early / Incidence not known
blurred vision / Early / Incidence not known

diarrhea / Early / 4.0-13.0
drowsiness / Early / 3.0-6.0
nasal congestion / Early / 4.0-6.0
fatigue / Early / 1.0-4.0
fever / Early / 4.0-4.0
cough / Delayed / 3.0-3.0
xerostomia / Early / 2.0-3.0
infection / Delayed / 1.6-3.0
pharyngitis / Delayed / 1.0-2.0
epistaxis / Delayed / 2.0-2.0
insomnia / Early / 1.2-1.2
pruritus / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
rash / Early / 0-1.0
weight gain / Delayed / 0.5-0.5
agitation / Early / 0.4-0.4
syncope / Early / 0.2-0.2
dizziness / Early / Incidence not known
arthralgia / Delayed / Incidence not known
tremor / Early / Incidence not known
asthenia / Delayed / Incidence not known
myalgia / Early / Incidence not known
vertigo / Early / Incidence not known
vomiting / Early / Incidence not known
dysgeusia / Early / Incidence not known
nausea / Early / Incidence not known
paresthesias / Delayed / Incidence not known

DRUG INTERACTIONS

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Pentazocine: (Moderate) Concurrent use of cetirizine/levocetirizine with pentazocine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Acetaminophen; Propoxyphene: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Alfentanil: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Alprazolam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Amobarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Amoxapine: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Anticholinergics: (Moderate) Concurrent use of cetirizine/levocetirizine with anticholinergics should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Apomorphine: (Moderate) Concurrent use of cetirizine/levocetirizine with apomorphine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Aripiprazole: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Asenapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Aspirin, ASA; Carisoprodol: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
atypical antipsychotic: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Baclofen: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Barbiturates: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzodiazepines: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Brexpiprazole: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Buprenorphine: (Major) Reserve concomitant prescribing of buprenorphine and cetirizine for use in patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Also monitor for signs of urinary retention or reduced gastric motility during concomitant use. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Buprenorphine; Naloxone: (Major) Reserve concomitant prescribing of buprenorphine and cetirizine for use in patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Also monitor for signs of urinary retention or reduced gastric motility during concomitant use. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Butabarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Butalbital; Acetaminophen: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Butorphanol: (Moderate) Concurrent use of cetirizine/levocetirizine with butorphanol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Concurrent use of cetirizine/levocetirizine with sodium oxybate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cannabidiol: (Moderate) Concurrent use of cetirizine/levocetirizine with cannabidiol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Capsaicin; Metaxalone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Carbidopa; Levodopa; Entacapone: (Moderate) Caution is recommended during concurrent use of cetirizine or levocetirizine with COMT inhibitors because of the possibility for additive sedative effects. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cariprazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Carisoprodol: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Celecoxib; Tramadol: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and cetirizine. Concurrent use may result in additive CNS depression.
Chloral Hydrate: (Moderate) Concurrent use of cetirizine/levocetirizine with chloral hydrate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlordiazepoxide: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlordiazepoxide; Amitriptyline: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlordiazepoxide; Clidinium: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorthalidone; Clonidine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Chlorzoxazone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Clonazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Clonidine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Clorazepate: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Clozapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
COMT inhibitors: (Moderate) Caution is recommended during concurrent use of cetirizine or levocetirizine with COMT inhibitors because of the possibility for additive sedative effects. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclobenzaprine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Dantrolene: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of cetirizine and ritonavir resulted in a 42% increase in the AUC, 53% increase in half-life, and 29% decrease in clearance of cetirizine. Cetirizine did not alter ritonavir disposition.
Desloratadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Desloratadine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Deutetrabenazine: (Moderate) Concurrent use of cetirizine/levocetirizine with deutetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Dexmedetomidine: (Moderate) Concurrent use of cetirizine/levocetirizine with dexmedetomidine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of dexmedetomidine; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Diazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dronabinol: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol.
Droperidol: (Moderate) Concurrent use of cetirizine/levocetirizine with droperidol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Enflurane: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Entacapone: (Moderate) Caution is recommended during concurrent use of cetirizine or levocetirizine with COMT inhibitors because of the possibility for additive sedative effects. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and cetirizine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Eszopiclone: (Moderate) Concurrent use of cetirizine/levocetirizine with eszopiclone should generally be avoided. Concurrent use of eszopiclone with other CNS depressants increases the risk for CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). If concurrent use is necessary, patients should be instructed to contact their provider immediately if these symptoms or behaviors occur.
Etomidate: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and cetirizine. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Flibanserin: (Moderate) Concurrent use of cetirizine/levocetirizine with flibanserin should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Flurazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Fospropofol: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Gabapentin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and gabapentin due to the risk for additive CNS depression.
General anesthetics: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Guanfacine: (Moderate) Concurrent use of cetirizine/levocetirizine with guanfacine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Haloperidol: (Moderate) Concurrent use of cetirizine/levocetirizine with haloperidol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Halothane: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Heparin: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
Heterocyclic antidepressants: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Concurrent use of cetirizine/levocetirizine with methyldopa should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Iloperidone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Isocarboxazid: (Moderate) Monitor for increased anticholinergic effects and unusual drowsiness and sedation during coadministration of cetirizine and monoamine oxidase inhibitors due to the risk for additive anticholinergic activity and CNS depression.
Isoflurane: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Ketamine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cetirizine. Dosage adjustments of lemborexant and cetirizine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levorphanol: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lofexidine: (Moderate) Concurrent use of cetirizine/levocetirizine with lofexidine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Lopinavir; Ritonavir: (Moderate) Coadministration of cetirizine and ritonavir resulted in a 42% increase in the AUC, 53% increase in half-life, and 29% decrease in clearance of cetirizine. Cetirizine did not alter ritonavir disposition.
Loratadine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
Loratadine; Pseudoephedrine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
Lorazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Loxapine: (Moderate) Concurrent use of cetirizine/levocetirizine with loxapine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Lumateperone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Lurasidone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Maprotiline: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Melatonin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and melatonin due to the risk for additive CNS depression.
Meperidine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Meperidine; Promethazine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Mephobarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Meprobamate: (Moderate) Concurrent use of cetirizine/levocetirizine with meprobamate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Metaxalone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Methadone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methohexital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Methyldopa: (Moderate) Concurrent use of cetirizine/levocetirizine with methyldopa should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Midazolam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Mirtazapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and mirtazapine due to the risk for additive CNS depression.
Molindone: (Moderate) Concurrent use of cetirizine/levocetirizine with molindone should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Monoamine oxidase inhibitors: (Moderate) Monitor for increased anticholinergic effects and unusual drowsiness and sedation during coadministration of cetirizine and monoamine oxidase inhibitors due to the risk for additive anticholinergic activity and CNS depression.
Morphine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Nabilone: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as nabilone.
Nalbuphine: (Moderate) Concurrent use of cetirizine/levocetirizine with nalbuphine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Nefazodone: (Moderate) Concurrent use of cetirizine/levocetirizine with nefazodone should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Nirmatrelvir; Ritonavir: (Moderate) Coadministration of cetirizine and ritonavir resulted in a 42% increase in the AUC, 53% increase in half-life, and 29% decrease in clearance of cetirizine. Cetirizine did not alter ritonavir disposition.
Olanzapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Olanzapine; Fluoxetine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Olanzapine; Samidorphan: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Oliceridine: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of cetirizine and ritonavir resulted in a 42% increase in the AUC, 53% increase in half-life, and 29% decrease in clearance of cetirizine. Cetirizine did not alter ritonavir disposition.
Opiate Agonists: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opicapone: (Moderate) Caution is recommended during concurrent use of cetirizine or levocetirizine with COMT inhibitors because of the possibility for additive sedative effects. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Oxazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Paliperidone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Pentazocine: (Moderate) Concurrent use of cetirizine/levocetirizine with pentazocine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Pentazocine; Naloxone: (Moderate) Concurrent use of cetirizine/levocetirizine with pentazocine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Pentobarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Perampanel: (Moderate) Concurrent use of cetirizine/levocetirizine with perampanel should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Phenelzine: (Moderate) Monitor for increased anticholinergic effects and unusual drowsiness and sedation during coadministration of cetirizine and monoamine oxidase inhibitors due to the risk for additive anticholinergic activity and CNS depression.
Phenobarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Pimavanserin: (Moderate) Concurrent use of cetirizine/levocetirizine with pimavanserin should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Pimozide: (Moderate) Concurrent use of cetirizine/levocetirizine with pimozide should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Pramipexole: (Moderate) Concurrent use of cetirizine/levocetirizine with pramipexole should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Pregabalin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and pregabalin due to the risk for additive CNS depression.
Primidone: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Propofol: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Propoxyphene: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Quazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Quetiapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Ramelteon: (Moderate) Concurrent use of cetirizine/levocetirizine with ramelton should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Rasagiline: (Moderate) Concurrent use of cetirizine/levocetirizine with rasagiline should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Remifentanil: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Remimazolam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Risperidone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Ritonavir: (Moderate) Coadministration of cetirizine and ritonavir resulted in a 42% increase in the AUC, 53% increase in half-life, and 29% decrease in clearance of cetirizine. Cetirizine did not alter ritonavir disposition.
Ropinirole: (Moderate) Concurrent use of cetirizine/levocetirizine with ropinirole should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Rotigotine: (Moderate) Concurrent use of cetirizine/levocetirizine with rotigotine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Safinamide: (Moderate) Concurrent use of cetirizine/levocetirizine with safinamide should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Secobarbital: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Sedating H1-blockers: (Moderate) Due to the duplicative and additive pharmacology, concurrent use of cetirizine/levocetirizine with sedating H1-blockers should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Selegiline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and selegiline due to the risk for additive CNS depression.
Sevoflurane: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent medications, including H1-blockers. False study results are possible; thorough patient history is important in the interpretation of procedure results.
Skeletal Muscle Relaxants: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Sodium Oxybate: (Moderate) Concurrent use of cetirizine/levocetirizine with sodium oxybate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Sufentanil: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Suvorexant: (Moderate) Concurrent use of cetirizine/levocetirizine with suvorexant should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Tapentadol: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tasimelteon: (Moderate) Concurrent use of cetirizine/levocetirizine with tasimelteon should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Temazepam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Tetrabenazine: (Moderate) Concurrent use of cetirizine/levocetirizine with tetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Thalidomide: (Moderate) Concurrent use of cetirizine/levocetirizine with thalidomide should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Theophylline, Aminophylline: (Minor) Large doses of aminophylline may reduce the clearance of cetirizine/levocetirizine. Monitor the patient clinically for an altered response to cetirizine/levocetirizine if coadministered with aminophylline. (Minor) Large doses of theophylline may reduce the clearance of cetirizine/levocetirizine. Monitor the patient clinically for increased cetirizine/levocetirizine-related adverse effects if coadministered with theophylline.
Thiopental: (Moderate) Concurrent use of cetirizine/levocetirizine with barbiturates should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Thiothixene: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Tolcapone: (Moderate) Caution is recommended during concurrent use of cetirizine or levocetirizine with COMT inhibitors because of the possibility for additive sedative effects. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tramadol: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tramadol; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cetirizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tranylcypromine: (Moderate) Monitor for increased anticholinergic effects and unusual drowsiness and sedation during coadministration of cetirizine and monoamine oxidase inhibitors due to the risk for additive anticholinergic activity and CNS depression.
Trazodone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and trazodone due to the risk for additive CNS depression.
Triazolam: (Moderate) Concurrent use of cetirizine/levocetirizine with benzodiazepines should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Tricyclic antidepressants: (Moderate) Concurrent use of cetirizine/levocetirizine with tricyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Trospium: (Moderate) Dry mouth and drowsiness may occur in patients receiving cetirizine/levocetirizine; caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
Valerian, Valeriana officinalis: (Moderate) Concurrent use of cetirizine/levocetirizine with valerian should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Valproic Acid, Divalproex Sodium: (Moderate) Concurrent use of cetirizine/levocetirizine with valproic acid should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Zaleplon: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and zaleplon due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary.
Ziprasidone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Zolpidem: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and zolpidem due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary. Limit the dose of Intermezzo sublingual tablets to 1.75 mg/day.

PREGNANCY AND LACTATION

Available data with levocetirizine use during human pregnancy are insufficient to determine any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of fetal harm with the administration of levocetirizine during organogenesis at doses greatly exceeding the maximum recommended human dose (MRHD) in adults (doses up to 390 and 470 times, respectively, in pregnant rats and rabbits); animal studies are not always indicative of human response.[33350] Self-medication with cetirizine (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and treatment recommendations. The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology consider cetirizine and loratadine as acceptable alternatives in pregnancy, preferably after the first trimester, when first-generation antihistamines are not tolerated.[46717]

There are no data available on the presence of levocetirizine in human milk, the effects on the breastfed infant, or the effects on milk production. Levocetirizine is the R-enantiomer of cetirizine. Cetirizine is excreted in human breast milk, but quantitative amounts are not known.[33350] Because of its lack of sedation and low milk concentrations, loratadine is not expected to cause adverse effects in breastfed babies and loratadine is usually considered compatible with breast-feeding.[27500] The British Society for Allergy and Clinical Immunology also recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women.[37820]

MECHANISM OF ACTION

Levocetirizine is highly selective for histamine H1-receptors. Levocetirizine, similar to other H1-antagonists, does not block the release of histamine, as do cromolyn and nedocromil, but rather competes with free histamine for binding at H1-receptor sites. This competitive antagonism blocks the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. In vitro studies have demonstrated that levocetirizine has a 2-fold higher affinity for the H1-receptors than cetirizine. Levocetirizine has a lower incidence of sedation compared to older antihistamines.
 
The inflammatory response plays a prominent role in the development of nasal obstruction in patients with allergic rhinitis and involves a number of mediators. Initial release of histamine from mast cells is followed by late-phase reactions involving a number of other cells, such as fibroblasts, epithelial cells, neutrophils, eosinophils (especially in conditions with raised IgE levels), macrophages, platelets, and lymphocytes. Cell adhesion can also be part of the inflammatory process. Levocetirizine has demonstrated anti-inflammatory effects in both in vitro and in vivo studies. The anti-inflammatory action appears to be related to a reduction in eosinophils, neutrophils, interleukin-4 and interleukin-8.

PHARMACOKINETICS

Levocetirizine is administered orally. It is 91—92% protein bound. Only 14% undergoes metabolism via aromatic oxidation, N-dealkylation, O-dealkylation, and taurine conjugation; the remaining 86% is excreted unchanged. The hepatic cytochrome P-450 (CYP) isoenzyme responsible for dealkylation is CYP3A4; the enzymes responsible for aromatic oxidation have not fully been elucidated. The elimination half-life in healthy volunteers was approximately 8—9 hours after administration of oral tablets or solution; urinary excretion accounts for 85.4% of a dose and the feces for 12.9%.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
In vitro studies demonstrate that levocetirizine does not inhibit CYP1A2, 2C9, 2C19, 2A1, 2D6, 2E1, or 3A4; nor does it induce CYP1A2, 2C9, or 3A4. Only 14% of levocetirizine is metabolized via aromatic oxidation, N-dealkylation, O-dealkylation and taurine conjugation. The CYP3A4 isoenzyme is responsible for dealkylation; the enzymes responsible for aromatic oxidation have not fully been elucidated.