Levocetirizine (levocetirizine dihydrochloride)

The manufacturer states that a 5-mg dose of levocetirizine dihydrochloride administered as the commercially available oral solution containing 2.5 mg/5 mL is bioequivalent to a 5-mg tablet.

Levocetirizine dihydrochloride is administered orally once daily in the evening without regard to meals. The drug is commercially available as tablets or an oral solution.

Levocetirizine tablets are scored and can be broken in half (each half providing a dose of 2.5 mg).

Levocetirizine dihydrochloride tablets should be stored at 20-25degreesC. Levocetirizine dihydrochloride oral solution should be stored at 20-25degreesC (excursions permitted to 15-30degreesC).

Levocetirizine is also commercially available in various over-the-counter (OTC) preparations. See the FDA Orange Book and the manufacturer's drug facts for information.

No formal drug interaction studies have been performed with levocetirizine to date; studies have been performed with racemic cetirizine.

Levocetirizine does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2C9, 2C19, 2A1, 2D6, 2E1, or 3A4. The drug does not induce uridine diphosphate-glucuronosyltransferase (UGT) 1A or CYP isoenzymes 1A2, 2C9, or 3A4. The manufacturer states that levocetirizine is unlikely to produce or be subject to pharmacokinetic interactions associated with metabolic enzyme systems.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That Affect Iodide/Radioactive Iodide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(2) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(3)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1)

Agents That Affect Iodide/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(3) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(4)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2)

There are no moderate interactions for this drug.

*Known hypersensitivity (e.g., urticaria, anaphylaxis) to levocetirizine or any ingredient in the formulation, or to cetirizine.

*Adults and pediatric patients 12 years of age and older with end-stage renal disease (creatinine clearance less than 10 mL/minute) or undergoing hemodialysis.

*Pediatric patients 6 months to 11 years of age with renal impairment.

• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

• Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min

There are no moderate contraindications for this drug.

Adverse effects reported in 2% or more of patients 12 years of age and older receiving levocetirizine dihydrochloride (2.5 or 5 mg daily) in clinical trials and occurring more frequently than placebo include somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis.

Adverse effects reported in 2% or more of pediatric patients 6-12 years of age receiving levocetirizine dihydrochloride (5 mg daily) in clinical trials and occurring more frequently than placebo include pyrexia, cough, somnolence, and epistaxis.

Adverse effects reported in 2% or more of pediatric patients 1-5 years of age receiving levocetirizine dihydrochloride (1.25 mg twice daily) in a safety trial and occurring more frequently than with placebo include pyrexia, diarrhea, vomiting, and otitis media.

Adverse effects reported in 3% or more of pediatric patients 6-11 months of age receiving levocetirizine dihydrochloride (1.25 mg once daily) in a safety trial and occurring more frequently than placebo include diarrhea and constipation.

Rare or Very Rare

• Acquired dystonia
• Acute generalized exanthematous pustulosis
• Anaphylaxis
• Angioedema
• Cholestasis
• Extrapyramidal disease
• Glomerulonephritis
• Hepatitis
• Oculogyric crisis
• Seizure disorder
• Suicidal ideation

More Frequent

• Cough
• Drowsy
• Epistaxis
• Fatigue
• General weakness
• Pharyngitis

Less Frequent

• Fever
• Xerostomia

Rare or Very Rare

• Aggressive behavior
• Agitation
• Arthralgia
• Blurred vision
• Constipation
• Depression
• Diarrhea
• Dizziness
• Dysgeusia
• Dyskinesia
• Dyspnea
• Dysuria
• Edema
• Hallucinations
• Hypotension
• Increased appetite
• Insomnia
• Motor tic disorder
• Myalgia
• Myoclonus
• Nausea
• Nightmares
• Palpitations
• Paresthesia
• Pruritus of skin
• Skin rash
• Syncope
• Tachycardia
• Tremor
• Urinary retention
• Urticaria
• Vertigo
• Visual changes
• Vomiting
• Weight gain

No enhanced messaging available.

Safety of levocetirizine has not been established in children younger than 6 months of age.

Efficacy of levocetirizine dihydrochloride 1.25 mg once daily (in pediatric patients 6 months to 5 years of age) and levocetirizine dihydrochloride 2.5 mg once daily (in pediatric patients 6-11 years of age) for the management of allergic rhinitis is based on extrapolation of the demonstrated efficacy of the 5-mg daily dosage in pediatric patients 12 years of age and older and on pharmacokinetic comparisons in adults and children.

Efficacy of levocetirizine dihydrochloride 1.25 mg once daily (in pediatric patients 6 months to 5 years of age), levocetirizine dihydrochloride 2.5 mg once daily (in pediatric patients 6-11 years of age), and levocetirizine dihydrochloride 5 mg once daily (in pediatric patients 12-17 years of age) for the management of chronic idiopathic urticaria is based on extrapolation of the demonstrated efficacy of the 5-mg daily dosage in adults and/or on pharmacokinetic comparisons in adults and children.

A cross-study comparison of pharmacokinetic data indicate that systemic exposure (i.e., AUC) to levocetirizine was approximately 2-fold higher in pediatric patients 6-11 years of age with seasonal allergic rhinitis receiving a single 5-mg dose compared with that reported in adults receiving the same dose. Data from a retrospective population pharmacokinetic analysis indicate that administration of levocetirizine dihydrochloride 1.25 mg once daily in children 6 months to 5 years of age results in plasma levocetirizine concentrations that are comparable to those observed in adults receiving the drug at a dosage of 5 mg once daily.

Available data are insufficient to establish a drug-associated risk of miscarriage, birth defects, or adverse maternal or fetal outcomes with levocetirizine use during pregnancy.

Animal reproductive studies have shown no evidence of fetal harm with administration of levocetirizine to pregnant rats and rabbits during the period of organogenesis at doses up to 390 times and 470 times, respectively, the maximum recommended human dose (MRHD). In mice who received cetirizine during late gestation and the lactation period, cetirizine administration at a dose 25 times the MRHD had no effects on pup development; however, lower pup weight was observed during lactation when a dose 95 times the MRHD was administered.

Levocetirizine is expected to be distributed into human milk (since cetirizine is distributed into milk). Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for levocetirizine and any potential adverse effects on the breast-fed child from levocetirizine or from the underlying maternal condition.

Dosage of levocetirizine should be selected with caution in geriatric patients (usually starting at the low end of the dosage range) because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.

Experience from clinical trials in patients 65 years of age and older is insufficient to determine whether geriatric patients respond differently than younger adults. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. Dosage of levocetirizine generally should be selected with caution in geriatric patients because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy. Periodic monitoring of renal function may be useful.