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  • CLASSES

    Second generation (non-sedating) 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

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For the management of symptoms of seasonal allergies or perennial allergies, including allergic rhinitis.
    Oral dosage (oral solution)
    Adults

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily. For geriatric patients, the FDA-approved product labeling recommends starting with the lowest dose.

    Children and Adolescents 12 to 17 years

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily.

    Children 6 to 11 years

    2.5 mg PO once daily in the evening. In some clinical studies, children 6 to 12 years received 5 mg PO once daily; however, the FDA-approved product labeling warns against exceeding 2.5 mg/day as systemic exposure after a 5 mg dose in this population is approximately twice that of adult patients.

    Infants and Children 6 months to 5 years

    1.25 mg PO once daily in the evening. Levocetirizine is FDA-approved for use in children 2 years of age and older for seasonal allergic rhinitis and for infants and children 6 months and older for perennial allergic rhinitis. The nonprescription (OTC) solution is labeled only for use in children 2 years of age and older.

    Oral dosage (oral tablet)
    Adults

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily. For geriatric patients, the FDA-approved product labeling recommends starting with the lowest dose.

    Children and Adolescents 12 to 17 years

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily.

    Children 6 to 11 years

    2.5 mg PO once daily in the evening. In some clinical studies, children 6 to 12 years received 5 mg PO once daily; however, the FDA-approved product labeling warns against exceeding 2.5 mg/day as systemic exposure after a 5 mg dose in this population is approximately twice that of adult patients.

    For the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria.
    Oral dosage (oral solution)
    Adults

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily. In geriatric patients, the manufacturer recommends starting with the lowest dose.

    Children and Adolescents 12 years and older

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily.

    Children 6 to 11 years

    2.5 mg PO once daily in the evening.

    Infants and Children 6 months to 5 years

    1.25 mg PO once daily in the evening.

    Oral dosage (oral tablet)
    Adults

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily. In geriatric patients, the manufacturer recommends starting with the lowest dose.

    Children and Adolescents 12 years and older

    5 mg PO once daily in the evening. Some patients may experience adequate symptom control with 2.5 mg PO once daily.

    Children 6 to 11 years

    2.5 mg PO once daily in the evening. 

    For the symptomatic treatment of atopic dermatitis†.
    Oral dosage (oral solution)
    Children 1 to 2 years

    0.125 mg/kg/dose PO twice daily. Total daily dosage range from clinical studies: 2.83 to 3.83 mg/day.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    5 mg/day PO.

    Geriatric

    5 mg/day PO.

    Adolescents

    5 mg/day PO.

    Children

    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.

    Infants

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

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed.

    Renal Impairment

    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

    Oral Administration

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

    Oral Solid Formulations

    Tablets: May be split in half.

    Oral Liquid Formulations

    Oral solution: Administer using a calibrated measuring device.

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

    CONTRAINDICATIONS / PRECAUTIONS

    Hydroxyzine hypersensitivity

    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.

    Dialysis, renal failure, renal impairment

    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.

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion

    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.

    Infants, neonates

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

    Pregnancy

    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]

    Breast-feeding

    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]

    Bladder obstruction, prostatic hypertrophy, urinary retention

    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.

    Geriatric

    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

    Severe

    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

    Moderate

    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

    Mild

    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; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression. (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.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Tramadol: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Alfentanil: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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.
    Amitriptyline; 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.
    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) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Asenapine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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: (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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression. (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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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; Carisoprodol: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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; Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    atypical antipsychotic: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Baclofen: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Buprenorphine: (Moderate) Concurrent use of cetirizine/levocetirizine with buprenorphine 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.
    Buprenorphine; Naloxone: (Moderate) Concurrent use of cetirizine/levocetirizine with buprenorphine 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.
    Buspirone: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    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.
    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.
    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) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    Carbidopa; Levodopa: (Moderate) Concurrent use of cetirizine/levocetirizine with levodopa 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.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concurrent use of cetirizine/levocetirizine with COMT inhibitors 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. (Moderate) Concurrent use of cetirizine/levocetirizine with levodopa 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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Cariprazine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Carisoprodol: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    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; 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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorthalidone; Clonidine: (Moderate) Concurrent use of cetirizine/levocetirizine with clonidine 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.
    Chlorzoxazone: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    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) Concurrent use of cetirizine/levocetirizine with clonidine 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.
    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) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Codeine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    COMT inhibitors: (Moderate) Concurrent use of cetirizine/levocetirizine with COMT inhibitors 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.
    Cyclobenzaprine: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    Dantrolene: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Concurrent use of cetirizine/levocetirizine with COMT inhibitors 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.
    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.
    Ethanol: (Moderate) Concurrent use of cetirizine/levocetirizine with alcohol should be avoided because additional reduction in mental alertness may occur. Caution patients about the simultaneous use of alcohol, and caution that the effects of alcohol may be increased.
    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.
    Fentanyl: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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.
    Fluoxetine; Olanzapine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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 excessive sedation and somnolence during coadministration of cetirizine and gabapentin. Concurrent use may result in 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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydromorphone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Iloperidone: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Isocarboxazid: (Major) Concurrent use of cetirizine/levocetirizine with MAOIs should generally be avoided. Coadministration may increase the risk of CNS depressant-related and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within 2 weeks of therapy with a MAOI.
    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.
    Levodopa: (Moderate) Concurrent use of cetirizine/levocetirizine with levodopa 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.
    Levorphanol: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Lurasidone: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    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.
    Meperidine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Meperidine; Promethazine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    Methadone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) 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.
    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: (Major) Concurrent use of cetirizine/levocetirizine with MAOIs should generally be avoided. Coadministration may increase the risk of CNS depressant-related and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within 2 weeks of therapy with a MAOI.
    Morphine: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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.
    Olanzapine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Orphenadrine: (Moderate) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Oxymorphone: (Moderate) Concomitant use of opioid agonists with cetirizine/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Paliperidone: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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: (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: (Major) Concurrent use of cetirizine/levocetirizine with MAOIs should generally be avoided. Coadministration may increase the risk of CNS depressant-related and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within 2 weeks of therapy with a MAOI.
    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.
    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 excessive sedation and somnolence during coadministration of cetirizine and pregabalin. Concurrent use may result in 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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Risperidone: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    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: (Major) Concurrent use of cetirizine/levocetirizine with MAOIs should generally be avoided. Coadministration may increase the risk of CNS depressant-related and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within 2 weeks of therapy with a MAOI.
    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) Concurrent use of cetirizine/levocetirizine with skeletal muscle relaxants 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.
    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/levocetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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 medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Concurrent use of cetirizine/levocetirizine with COMT inhibitors 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.
    Tramadol: (Moderate) Concomitant use of opioid agonists with cetirizine may cause excessive sedation and somnolence. Limit the use of opioid pain medications 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. Educate patients about the risks and symptoms of excessive CNS depression.
    Tranylcypromine: (Major) Concurrent use of cetirizine/levocetirizine with MAOIs should generally be avoided. Coadministration may increase the risk of CNS depressant-related and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within 2 weeks of therapy with a MAOI.
    Trazodone: (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.
    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) Concurrent use of cetirizine/levocetirizine with zaleplon should generally be avoided. Concurrent use of zaleplon 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.
    Ziprasidone: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics 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.
    Zolpidem: (Moderate) Concurrent use of cetirizine/levocetirizine with zolpidem should generally be avoided. Concurrent use of zolpidem 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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.
     

    Oral Route

    The oral tablet and oral solution are bioequivalent. Levocetirizine has a rapid onset with peak plasma concentrations reached in 0.9 hours and 0.5 hours after administration of the oral tablet and oral solution, respectively. Steady state plasma concentrations are achieved in 2 days. Although the rate of absorption of the tablets may be increased and peak plasma concentrations reduced by 36% when administered with food, levocetirizine may be administered with or without food.