Levocetirizine

Pharmacologic Category

Histamine H₁ Antagonist; Histamine H₁ Antagonist, Second Generation; Piperazine Derivative

Dosing: Adult

Chronic idiopathic urticaria: Oral: 5 mg once daily (in the evening); some patients may experience relief of symptoms with 2.5 mg once daily. In one clinical trial, the titrated use of higher doses (up to 10 mg twice daily) in adults demonstrated clinical improvement (Staevska 2010).

Allergic rhinitis (OTC only): Oral: 5 mg once daily (in the evening); some patients with less severe symptoms may experience relief with 2.5 mg once daily; maximum dose: 5 mg/day

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing; dosing should begin at the lower end of the dosing range.

Dosing: Renal Impairment: Adult

Chronic idiopathic urticaria, perennial allergic rhinitis:

CrCl 50 to 80 mL/minute: 2.5 mg once daily

CrCl 30 to 50 mL/minute: 2.5 mg once every other day

CrCl 10 to 30 mL/minute: 2.5 mg twice weekly (every 3 or 4 days)

CrCl <10 mL/minute, hemodialysis patients: Use is contraindicated.

Hemodialysis: Nondialyzable

Allergic rhinitis (OTC): Use is not recommended.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

Allergic rhinitis, perennial: Oral:

Infants ≥6 months and Children ≤5 years: 1.25 mg once daily (in the evening); maximum daily dose: 1.25 mg/day; Note: In children >2 years, dosing based on previous FDA approved manufacturer labeling (Xyzal prescribing information January 2016)

Children ≥6 years and Adolescents: Note: Dosing based on previous FDA approved manufacturer labeling (Xyzal prescribing information January 2016):

6 to 11 years: 2.5 mg once daily (in the evening); maximum daily dose: 2.5 mg/day

≥12 years: 5 mg once daily (in the evening); some patients may experience relief of symptoms with 2.5 mg once daily

Hay fever and other respiratory allergies: OTC labeling: Oral:

Children 2 to 5 years: 1.25 mg once daily (in the evening); maximum daily dose: 1.25 mg/day

Children 6 to 11 years: 2.5 mg once daily (in the evening); maximum daily dose: 2.5 mg/day

Children ≥12 years and Adolescents: 2.5 to 5 mg once daily (in the evening); dose based on symptom severity; maximum daily dose: 5 mg/day

Urticaria, chronic: Oral:

Infants ≥6 months and Children ≤5 years: 1.25 mg once daily (in the evening); maximum daily dose: 1.25 mg/day

Children 6 to 11 years: 2.5 mg once daily (in the evening); maximum daily dose: 2.5 mg/day

Children ≥12 years and Adolescents: 5 mg once daily (in the evening); some patients may experience relief of symptoms with 2.5 mg once daily

Dosing: Renal Impairment: Pediatric

Allergic perennial rhinitis, chronic urticaria:

Infants ≥6 months and Children ≤11 years: Contraindicated with any degree of renal impairment.

Children ≥12 years and Adolescents:

CrCl >80 mL/minute: No adjustment necessary

CrCl 50 to 80 mL/minute: 2.5 mg once daily

CrCl 30 to 50 mL/minute: 2.5 mg once every other day

CrCl 10 to 30 mL/minute: 2.5 mg twice weekly (every 3 or 4 days)

CrCl <10 mL/minute or on hemodialysis: Contraindicated

Hemodialysis: Nondialyzable

Hay fever and other respiratory allergies (OTC): Children ≥2 years and Adolescents: Use is not recommended.

Dosing: Hepatic Impairment: Pediatric

Infants ≥6 months, Children, and Adolescents: No dosage adjustment necessary.

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Chronic idiopathic urticaria: Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in adults and pediatric patients 6 months and older

Perennial allergic rhinitis: Relief of symptoms associated with perennial allergic rhinitis in adults and pediatric patients 6 months to 2 years

Allergic rhinitis (OTC only): Temporary relief of symptoms due to hay fever or other respiratory allergies (including rhinitis, sneezing, itchy/watery eyes, or itching of the throat/nose) in adults and pediatric patients 2 years and older

* See Uses in AHFS Essentials for additional information.

Class and Related Monographs

Antihistamines

Comparative Efficacy

• LEVOCETIRIZINE DIHYDROCHLORIDE

Clinical Practice Guidelines

Allergic Rhinitis:

AAO-HNS, “Clinical Practice Guideline: Allergic Rhinitis,” 2015

Urticaria:

EAACI/GA²LEN/EDF/WAO, “Guideline for the Definition, Classification, Diagnosis and Management of Urticaria - 2017 Update,” April 2018

Administration: Oral

Administer in the evening with or without food. Use an accurate measuring device for the oral solution; a household teaspoon is not an accurate measuring device.

Administration: Pediatric

Oral: Administer without regard to food in the evening.

Storage/Stability

Xyzal: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Xyzal (OTC): Store at 20°C to 25°C (68°F to 77°F)

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to ease allergy signs.

• It is used to treat hives.

Frequently reported side effects of this drug

• Loss of strength and energy

• Fatigue

• Stuffy nose

• Sore throat

• Nosebleed

• Dry mouth

• Cough

• Vomiting

• Constipation

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Ear pain

• Difficult urination

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Known hypersensitivity to levocetirizine, cetirizine, or any component of the formulation; end-stage renal disease (CrCl <10 mL/minute); hemodialysis; infants and children 6 months to 11 years of age with renal impairment

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Pruritus: Rebound pruritus may occur within several days after stopping cetirizine, usually after long-term (eg, months to years) use.

Disease-related concerns:

• Renal impairment: Levocetirizine is excreted primarily by the kidneys; use with caution in adults with mild to severe renal impairment; dosage adjustments may be needed. Use is contraindicated in end-stage renal disease (CrCl <10 mL/minute), patients undergoing hemodialysis, and in infants and children 6 months to 11 years of age with renal impairment.

• Urinary retention: Urinary retention may occur; use with caution in patients with increased risk of urinary retention (including spinal cord lesions or prostatic hyperplasia); discontinue if urinary retention occurs.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Use with caution in the elderly due to potential sedative effects. Dosage should be adjusted based on renal function.

Warnings: Additional Pediatric Considerations

Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; the AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported. Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient (AAP 2018; CDC 2007; FDA 2017; FDA 2018).

Pregnancy Considerations

Guidelines for the use of antihistamines in the treatment of allergic rhinitis or urticaria in pregnancy are generally the same as in nonpregnant females. Second generation antihistamines may be used for the treatment of allergic rhinitis and urticaria during pregnancy; however, information related to the use of levocetirizine in pregnancy is limited and other medications may be preferred (Wallace 2008; Zuberbier 2018).

Levocetirizine is the active enantiomer of cetirizine; refer to the cetirizine monograph for additional information.

Breast-Feeding Considerations

It is not known if levocetirizine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Levocetirizine is the active enantiomer of cetirizine which is present in breast milk; refer to the cetirizine monograph for additional information

Lexicomp Pregnancy & Lactation, In-Depth

• Levocetirizine

Briggs' Drugs in Pregnancy & Lactation

• Levocetirizine

Adverse Reactions

>10%: Gastrointestinal: Diarrhea (infants: 13%; children: 4%)

1% to 10%:

Central nervous system: Drowsiness (3% to 6%), fatigue (adolescents and adults: 4%)

Gastrointestinal: Constipation (infants: 7%), vomiting (4%), xerostomia (adolescents and adults: 2% to 3%)

Otic: Otitis media (children: 3%)

Respiratory: Nasopharyngitis (adolescents and adults: 4% to 6%), cough (children: 3%), epistaxis (children: 2%), pharyngitis (adolescents and adults: 2%)

Miscellaneous: Fever (children: 4%)

Frequency not defined: Neuromuscular & skeletal: Weakness

<1%, postmarketing, and/or case reports: Aggressive behavior, agitation, anaphylaxis, angioedema, arthralgia, blurred vision, depression, dizziness, dysgeusia, dyspnea, dysuria, edema, febrile seizures, fixed drug eruption, hallucination, hepatitis, hypersensitivity reaction, increased appetite, increased serum bilirubin, increased serum transaminases, insomnia, movement disorder (including dystonia and oculogyric crisis), myalgia, nausea, nightmares, palpitations, paresthesia, pruritus, seizure, skin rash, suicidal ideation, syncope, tachycardia, tremor, urinary retention, urticaria, vertigo, visual disturbances, weight gain

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• H₁ Antihistamine Allergy

Toxicology

• Histamine H₁ Antagonists, Second Generation

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk D: Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Monitoring Parameters

Creatinine clearance (prior to treatment for dosing adjustment)

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Oral, as dihydrochloride:

Xyzal: 2.5 mg/5 mL (148 mL [DSC]) [contains methylparaben, propylparaben, saccharin]

Xyzal Allergy 24HR Childrens: 2.5 mg/5 mL (148 mL) [alcohol free, dye free; contains methylparaben, propylparaben, saccharin; tutti-frutti flavor]

Generic: 2.5 mg/5 mL (118 mL, 148 mL)

Tablet, Oral, as dihydrochloride:

Xyzal: 5 mg [DSC] [scored]

Xyzal Allergy 24HR: 5 mg [scored]

Generic: 5 mg

Anatomic Therapeutic Chemical (ATC) Classification

• R06AE09

Generic Available (US)

Yes

Pricing: US

Solution (Levocetirizine Dihydrochloride Oral)

2.5 mg/5 mL (per mL): $0.62

Solution (Xyzal Allergy 24HR Childrens Oral)

2.5 mg/5 mL (per mL): $0.07

Tablets (Levocetirizine Dihydrochloride Oral)

5 mg (per each): $0.24 - $3.08

Tablets (Xyzal Allergy 24HR Oral)

5 mg (per each): $0.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Levocetirizine is an antihistamine which selectively competes with histamine for H₁-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. Levocetirizine, the active enantiomer of cetirizine, has twice the binding affinity at the H₁-receptor compared to cetirizine.

Pharmacodynamics/Kinetics

Onset of action: 1 hour (Devillier 2008)

Duration: 24 hours (Devillier 2008)

Absorption: Rapid and extensive

Distribution: V_d: Children 1 to 2 years: Oral solution: 0.37 ± 0.06 L/kg (Cranswick 2005); Children 6 to 11 years: Oral tablet: 0.4 ± 0.02 L/kg (Simons 2005); Adults: ~0.4 L/kg

Protein binding: 91% to 92%

Metabolism: Minimal (<14%); via aromatic oxidation, N and O-dealkylation (via CYPA4), and taurine conjugation

Half-life elimination: Children 1 to 2 years: Oral solution: 4.09 ± 0.67 hours (Cranswick 2005); Children 6 to 11 years: Oral tablet: 5.7 ± 0.2 hours (Simons 2005); Adults: ~8 to 9 hours

Time to peak, plasma: Children 1 to 2 years: Oral solution: Median: 1 hour (range: 1 to 6 hours) (Cranswick 2005); Children 6 to 11 years: Oral tablet: 1.2 ± 0.2 hours (Simons 2005); Adults: Oral solution: 0.5 hours, Tablet: 0.9 hours

Excretion: Urine (85.4 %); feces (12.9%)

Clearance: Children 1 to 2 years: Oral solution: 1.05 ± 0.1 mL/minute/kg (Cranswick 2005); Children 6 to 11 years: Oral tablet: 0.82 ± 0.05 mL/minute/kg (Simons 2005); Adults: 0.63 mL/kg/minute

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: In patients with mild, moderate, severe renal impairment, and end-stage renal disease, the AUC increased by 1.8, 3.2, 4.3, and 5.7-fold, respectively, and the half-life increased by 1.4, 2, 2.9, and 4-fold, respectively.

Geriatric: Total body Cl was approximately 33% lower in 9 elderly subjects, compared with younger adults.

Gender: Half-life was slightly shorter in women than in men; however, the body weight–adjusted oral Cl in women appears to be comparable with that in men.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

No information available to require special precautions

Index Terms

Levocetirizine Dihydrochloride

FDA Approval Date

May 25, 2007

References

American Academy of Pediatrics (AAP). Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. Updated June 12, 2018. Available at http://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/

Centers for Disease Control and Prevention (CDC). Infant deaths associated with cough and cold medications--two states, 2005. MMWR Morb Mortal Wkly Rep. 2007;56(1):1-4.[PubMed 17218934]

Cranswick N, Turzíkova J, Fuchs M, et al. Levocetirizine in 1-2 year old children: pharmacokinetic and pharmacodynamic profile. Int J Clin Pharmacol Ther. 2005;43(4):172-177.[PubMed 15966463]

Devillier P, Roche N, Faisy C. Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-230.[PubMed 18336052 ]

Food and Drug Administration (FDA). Most young children with a cough or cold don't need medicines. July 18, 2017. Available at https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm422465.htm. Last accessed November 2, 2018.

Food and Drug Administration (FDA). Use caution when giving cough and cold products to kids. Updated February 8, 2018. Available at https://www.fda.gov/drugs/resourcesforyou/specialfeatures/ucm263948.htm. Last accessed November 2, 2018.

Levocetirizine [prescribing information]. Livonia, MI: Rugby Laboratories; February 2018.

Nettis E, Colanardi MC, Barra L, et al, “Levocetirizine in the Treatment of Chronic Idiopathic Urticaria: A Randomized, Double-Blind, Placebo-Controlled Study,” Br J Dermatol, 2006, 154(3):533-8.[PubMed 16445787]

Simons FE and Simons KJ. Levocetirizine: Pharmacokinetics and Pharmacodynamics in Children Age 6 to 11 Years. J Allergy Clin Immunol. 2005;116(2):355-361.[PubMed 16083790]

Staevska, M, Popov T, Kralimarkova T, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125(3):676-682.[PubMed 20226302]

Wallace DV, Dykewicz MS, Bernstein DI, et al, "The Diagnosis and Management of Rhinitis: An Updated Practice Parameter," J Allergy Clin Immunol, 2008, 122(2 Suppl):1-84.[PubMed 18662584]

Xyzal (levetiracetam) [prescribing information]. Smyrna, GA: UCB, Inc; January 2016.

Xyzal (levocetirizine dihydrochloride) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis, US, LLC; April 2019.

Xyzal Allergy 24HR (levocetirizine dihydrochloride) [prescribing information]. Chattanooga, TN: Chattem, Inc; February 2017.

Xyzal Children’s Allergy 24HR (levocetirizine dihydrochloride) [prescribing information]. Chattanooga, TN: Chattem, Inc; February 2017.

Xyzal Children's liquid (levocetirizine dihydrochloride) [prescribing information]. Chattanooga, TN: Chattem, Inc.; February 2017.

Xyzal Children's tablet (levocetirizine dihydrochloride) [prescribing information]. Chattanooga, TN: Chattem, Inc.; February 2017.

Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414.[PubMed 29336054]

Brand Names: International

Alergocit (PK); Alermax (PY); Aleron (UA); Alerzin (UA); Allear (EG); Allergostop (LK); Allerzal (SG); Allerzet (PH); Allezal F.C. (SG); Antiss (CO); Aralevo (ES, LB); Calivida (LB); Cetimer (EC); Cetizal (RO, TH); Cetriler (PE); Cetrilev (UA); Cevozin (BD); Cipen (KR); Coalbi (KR); Curin (BD); Degraler (CL, EC, PE); Degraler Forte (EC); Ellezin (TH); Enacet (BD); Getcet (PH); Glencet (MY); Histaplen (BR, UY); L-Cet (BH); L-Falergi (ID); L-Zet (PH); Lerex (BD); Lertazin (VN); Letrizine (PH); Levocen (KR); Levocet (BR, EC, IN, TH); Levocezal (KR); Levomine (AR); Levorid (LK); Levozine (TW); Levrix (NZ); Levtrizin (TH); Lezat (CO); Lezinsan 5 (VN); Libbera (PE); Lisinex (HK); Locemine (TW); NeoAlertop (PY); Newzal (KR); Rinozal (IE); Seasonix (LK); Sensitin (PH); Singkast (TH); Tecovel (PH); Vocet (BD); Xaltec (EG); Xazal (ES); Xozal (GR); Xusal (DE, MX); Xuzal (CR, DO, EC, GT, HN, NI, PA, SV); Xyzal (AE, BB, BG, BH, CH, CN, CY, CZ, DE, DK, EE, FI, FR, GB, HK, HR, HU, ID, IE, IT, JO, JP, KR, KW, LB, LK, LT, MT, MY, NL, NO, PH, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, TH, TR, TW, UA, VN); Xyzall (AT, BE, LU); Xyzine (TW); Zalkevor (EG); Zenaro (RO); Zobral (TR); Zyller (TH); Zyxem (MX)

Last Updated 2/20/20