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Levocetirizine


General


Pronunciation

(LEE vo se TI ra zeen)


Brand Names: U.S.

  • Xyzal

Indications


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 and older

Seasonal allergic rhinitis: Relief of symptoms associated with seasonal allergic rhinitis in adults and pediatric patients 2 years and older


Contraindications


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


Dosing and Administration


Dosing: Adult

Allergic rhinitis, seasonal allergic rhinitis: Oral: 5 mg once daily (in the evening); some patients may experience relief of symptoms with 2.5 mg once daily.

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).


Dosing: Geriatric

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


Dosing: Pediatric

Perennial allergic rhinitis, chronic urticaria: Oral:

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

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

Children ≥12 years and Adolescents: Refer to adult dosing.

Seasonal allergic rhinitis: Oral:

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

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

Children ≥12 years and Adolescents: Refer to adult dosing.


Dosing: Renal Impairment

Children ≥12 years, Adolescents, and Adults:

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.

Children 6 months to 11 years with renal impairment: Use is contraindicated.

Hemodialysis: Nondialyzable


Dosing: Hepatic Impairment

No dosage adjustment necessary.


Administration

Oral: Administer in the evening without regard to meals.


Storage

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).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral, as dihydrochloride:

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

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

Tablet, Oral, as dihydrochloride:

Xyzal: 5 mg [scored]

Generic: 5 mg


Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

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

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

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

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

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Consider therapy modification

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

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

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

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

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

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

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

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. 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. Monitor therapy

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

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

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

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

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

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). 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. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

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

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

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

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

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

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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

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

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

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

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

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

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

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. 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. Consider therapy modification

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

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. Avoid combination

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

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

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

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

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

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

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

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. 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. 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. 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. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

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

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

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

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

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

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

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. 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. Consider therapy modification


Monitoring Parameters

Creatinine clearance (prior to treatment for dosing adjustment)


Adverse Reactions


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

1% to 10%:

Central nervous system: Drowsiness (3% to 6%), fatigue (adolescents and adults: 1% to 4%)

Gastrointestinal: Constipation (infants: 7%), vomiting (children: 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: 1% to 2%)

Miscellaneous: Fever (children: 4%)

Frequency not defined: Neuromuscular & skeletal: Weakness

<1% (Limited to important or life-threatening): Aggressive behavior, agitation, anaphylaxis, angioedema, arthralgia, convulsions, depression, dysuria, fixed drug eruption, hallucination, hepatitis, hypersensitivity reaction, increased serum bilirubin, increased serum transaminases, movement disorder (including dystonia and oculogyric crisis), myalgia, palpitations, paresthesia, pruritus, skin rash, suicidal ideation, syncope, tachycardia, urinary retention, urticaria, visual disturbances


Warnings/Precautions


Special Populations: 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.


Special Populations: Elderly

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


Special Populations: 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.


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).

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.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies; therefore, the manufacturer classifies levocetirizine as pregnancy category B. The use of antihistamines for the treatment of rhinitis during pregnancy is generally considered to be safe at recommended doses. Information related to the use of levocetirizine during pregnancy is limited; therefore, other agents are preferred. Levocetirizine is the active enantiomer of cetirizine; refer to the Cetirizine monograph for additional information.


Actions


Pharmacology

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.


Absorption

Rapid and extensive


Distribution

Vd: 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


Metabolism

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


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


Onset of Action

1 hour (Devillier 2008)


Time to Peak

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


Duration of Action

24 hours (Devillier 2008)


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


Protein Binding

91% to 92%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience fatigue, rhinitis, pharyngitis, or diarrhea (children). Have patient report immediately to prescriber severe loss of strength and energy, urinary retention, or change in amount of urine passed (HCAHPS).

- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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