Levocetirizine

Name: Levocetirizine

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Brand names

  • Xyzal®

Levocetirizine and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

Levocetirizine is assumed to be excreted in human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using levocetirizine.

Levocetirizine Usage

Take levocetirizine exactly as prescribed.

Levocetirizine comes in tablet and oral solution (liquid) forms. It is usually taken once daily in the evening.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take 2 doses of levocetirizine at the same time.

What should I discuss with my healthcare provider before taking levocetirizine?

You should not use this medicine if you are allergic to levocetirizine or cetirizine (Zyrtec).

You should not take levocetirizine if you have end-stage kidney disease or if you are on dialysis. Any child younger than 12 years old with kidney disease should not take levocetirizine.

To make sure levocetirizine is safe for you, tell your doctor if you have:

  • kidney disease;

  • liver disease;

  • urination problems (caused by conditions such as enlarged prostate or spinal cord lesion); or

  • gallbladder problems.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Levocetirizine can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Levocetirizine is not approved for use by anyone younger than 6 months old.

Before Using levocetirizine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For levocetirizine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to levocetirizine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of levocetirizine in children. Safety and efficacy have not been established in infants younger than 6 months of age.

Use in children 6 months to 11 years of age with kidney disease is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of levocetirizine in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving levocetirizine.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of levocetirizine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Enlarged prostate or
  • Lesions in the spinal cord—Use with caution. May increase risk for urinary retention.
  • Kidney disease—Use with caution. The effects of levocetirizine may be increased because of slower removal from the body.
  • Kidney disease, severe or
  • Kidney failure—Should not be used in patients with these conditions.
  • Urinary retention (problem passing urine)—Use with caution. May make this condition worse.

Precautions While Using levocetirizine

If your symptoms do not improve within a few days or if they become worse, check with your doctor.

levocetirizine may cause some people to become dizzy, drowsy, or less alert than they are normally. Make sure you know how you react to levocetirizine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

levocetirizine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for seizures, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor or dentist before taking any of the above while you are taking levocetirizine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Drug Interactions

In vitro data indicate that Levocetirizine is unlikely to produce pharmacokinetic interactions through inhibition or induction of liver drug metabolizing enzymes. No in vivo drug-drug interaction studies have been performed with Levocetirizine. Drug interaction studies have been performed with racemic cetirizine.
7.1 Antipyrine, Azithromycin, Cimetidine, Erythromycin, Ketoconazole, Theophylline, and Pseudoephedrine
Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole, and cimetidine. There was a small decrease (~16%) in the clearance of cetirizine caused by a 400 mg dose of theophylline. It is possible that higher theophylline doses could have a greater effect.
7.2 Ritonavir
Ritonavir increased the plasma AUC of cetirizine by about 42% accompanied by an increase in half-life (53%) and a decrease in clearance (29%) of cetirizine. The disposition of ritonavir was not altered by concomitant cetirizine administration.

Overdosage

Overdosage has been reported with Levocetirizine dihydrochloride.
Symptoms of overdose may include drowsiness in adults. In children agitation and restlessness may initially occur, followed by drowsiness. There is no known specific antidote to Levocetirizine dihydrochloride. Should overdose occur, symptomatic or supportive treatment is recommended. Levocetirizine dihydrochloride is not effectively removed by dialysis, and dialysis will be ineffective unless a dialyzable agent has been concomitantly ingested.
The acute maximal non-lethal oral dose of Levocetirizine was 240 mg/kg in mice (approximately 190 times the maximum recommended daily oral dose in adults, approximately 230 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 180 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m 2 basis). In rats the maximal non-lethal oral dose was 240 mg/kg (approximately 390 times the maximum recommended daily oral dose in adults, approximately 460 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 370 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m 2 basis).

Clinical Studies

14.1 Perennial Allergic Rhinitis
Adults and Adolescents 12 Years of Age and Older

The efficacy of Levocetirizine dihydrochloride was evaluated in four randomized, placebo-controlled, double-blind clinical trials in adult and adolescent patients 12 years and older with symptoms of perennial allergic rhinitis. The four clinical trials include two dose-ranging trials of 4 weeks duration and two efficacy trials (one 6-week and one 6-month) in patients with perennial allergic rhinitis.

These trials included a total of 1,729 patients (752 males and 977 females) of whom 227 were adolescents 12 to 17 years of age. Efficacy was assessed using a total symptom score from patient recording of 4 symptoms (sneezing, rhinorrhea, nasal pruritus, and ocular pruritus) in three studies and 5 symptoms (sneezing, rhinorrhea, nasal pruritus, ocular pruritus, and nasal congestion) in one study. Patients recorded symptoms using a 0 to 3 categorical severity scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe) once daily in the evening reflective of the 24 hour treatment period. The primary endpoint was the mean total symptom score averaged over the first week and over 4 weeks for perennial allergic rhinitis trials.

The two dose-ranging trials were conducted to evaluate the efficacy of Levocetirizine dihydrochloride 2.5 mg, 5 mg, and 10 mg once daily in the evening. These trials were 4 weeks in duration and included patients with perennial allergic rhinitis. In these trials, each of the three doses of Levocetirizine dihydrochloride demonstrated greater decrease in the reflective total symptom score than placebo and the difference was statistically significant for all three doses in the two studies. Results for one of these trials are shown in Table 4.


Table 4 Mean Reflective Total Symptom Score* in Allergic Rhinitis Dose-Ranging Trials

Treatment

N

Baseline

On Treatment Adjusted Mean

Difference from Placebo

Estimate

95% CI

p-value

Perennial Allergic Rhinitis Trial – Reflective total symptom score

Levocetirizine dihydrochloride 2.5 mg

133

7.14

4.12

1.17

(0.71, 1.63)

<0.001

Levocetirizine dihydrochloride 5 mg

127

7.18

4.07

1.22

(0.76, 1.69)

<0.001

Levocetirizine dihydrochloride 10 mg

129

7.58

4.19

1.10

(0.64, 1.57)

<0.001

Placebo

128

7.22

5.29

*Total symptom score is the sum of individual symptoms of sneezing, rhinorrhea, nasal pruritus, and ocular pruritus as assessed by patients on a 0-3 categorical severity scale.

One clinical trial evaluated the efficacy of Levocetirizine dihydrochloride 5 mg once daily in the evening compared to placebo in patients with perennial allergic rhinitis over a 6-week treatment period. Another trial conducted over a 6-month treatment period assessed efficacy at 4 weeks. Levocetirizine dihydrochloride 5 mg demonstrated a greater decrease from baseline in the reflective total symptom score than placebo and the difference from placebo was statistically significant. Results of the former are shown in Table 5.

Table 5 Mean Reflective Total Symptom Score* in Allergic Rhinitis Trials

Treatment

N

Baseline

On Treatment Adjusted Mean

Difference from Placebo

Estimate

95% CI

p-value

Perennial Allergic Rhinitis Trial – Reflective total symptom score

Levocetirizine dihydrochloride 5 mg

150

7.69

3.93

1.17

(0.70, 1.64)

<0.001

Placebo

142

7.44

5.10


*Total symptom score is the sum of individual symptoms of sneezing, rhinorrhea, nasal pruritus, and ocular pruritus as assessed by patients on a 0-3 categorical severity scale.

Onset of action was evaluated in two environmental exposure unit studies in allergic rhinitis patients with a single dose of Levocetirizine dihydrochloride 2.5 mg or 5 mg. Levocetirizine dihydrochloride 5 mg was found to have an onset of action 1 hour after oral intake. Onset of action was also assessed from the daily recording of symptoms in the evening before dosing in the allergic rhinitis trials. In these trials, onset of effect was seen after 1 day of dosing.


Pediatric Patients Less than 12 Years of Age
There are no clinical efficacy trials with Levocetirizine dihydrochloride 2.5 mg once daily in pediatric patients under 12 years of age, and no clinical efficacy trials with Levocetirizine dihydrochloride 1.25 mg once daily in pediatric patients 6 months to 5 years of age. The clinical efficacy of Levocetirizine dihydrochloride in pediatric patients under 12 years of age has been extrapolated from adult clinical efficacy trials based on pharmacokinetic comparisons [see Use in Specific Populations (8.4)]
14.2 Chronic Idiopathic Urticaria
Adult Patients 18 Years of Age and Older
The efficacy of Levocetirizine dihydrochloride for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria was evaluated in two multi-center, randomized, placebo-controlled, double-blind clinical trials of 4 weeks duration in adult patients 18 to 85 years of age with chronic idiopathic urticaria. The two trials included one 4-week dose-ranging trial and one 4-week single-dose level efficacy trial. These trials included 423 patients (139 males and 284 females). Most patients (>90%) were Caucasian and the mean age was 41. Of these patients, 146 received Levocetirizine dihydrochloride 5 mg once daily in the evening. Efficacy was assessed based on patient recording of pruritus severity on a severity score of 0 to 3 (0 = none to 3 = severe). The primary efficacy endpoint was the mean reflective pruritus severity score over the first week and over the entire treatment period. Additional efficacy variables were the instantaneous pruritus severity score, the number and size of wheals, and duration of pruritus.
The dose-ranging trial was conducted to evaluate the efficacy of Levocetirizine dihydrochloride 2.5 mg, 5 mg, and 10 mg once daily in the evening. In this trial, each of the three doses of Levocetirizine dihydrochloride demonstrated greater decrease in the reflective pruritus severity score than placebo and the difference was statistically significant for all three doses (see Table 6).
The single dose level trial evaluated the efficacy of Levocetirizine dihydrochloride 5 mg once daily in the evening compared to placebo in patients with chronic idiopathic urticaria over a 4-week treatment period. Levocetirizine dihydrochloride 5 mg demonstrated a greater decrease from baseline in the reflective pruritus severity score than placebo and the difference from placebo was statistically significant.
Duration of pruritus, number and size of wheals, and instantaneous pruritus severity score also showed significant improvement over placebo. The significant improvement in the instantaneous pruritus severity score over placebo confirmed end of dosing interval efficacy (see Table 6).

Table 6 Mean Reflective Pruritus Severity Score in Chronic Idiopathic Urticaria Trials

Treatment

N

Baseline

On Treatment Adjusted Mean

Different from Placebo

Estimate

95%Cl

p-value

Dose-Ranging Trial – Reflective pruritus severity score

Levocetirizine dihydrochloride

2.5mg

69

2.08

1.02

0.82

(0.58, 1.06)

<0.001

Levocetirizine dihydrochloride

5mg

62

2.07

0.92

0.91

(0.66, 1.16)

<0.001

Levocetirizine dihydrochloride

10mg

55

2.04

0.73

1.11

(0.85, 1.37)

<0.001

Placebo

60

2.25

1.84

Chronic Idiopathic Urticaria Trial – Reflective pruritus severity score

Levocetirizine dihydrochloride

5mg

80

2.07

0.94

0.62

(0.38, 0.86)

<0.001

Placebo

82

2.06

1.56


Pediatric Patients
There are no clinical efficacy trials in pediatric patients with chronic idiopathic urticaria [see Use in Specific Populations (8.4)].

Index Terms

  • Levocetirizine Dihydrochloride

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%

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

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 loss of strength and energy, fatigue, rhinitis, pharyngitis, constipation, or diarrhea. Have patient report immediately to prescriber difficult urination (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.

Usual Pediatric Dose for Allergic Rhinitis

Seasonal Allergic Rhinitis:
2 to 5 years: 1.25 mg orally once a day in the evening
6 to 11 years: 2.5 mg orally once a day in the evening
12 years or older: 5 mg orally once a day in the evening; some patients may be adequately controlled on 2.5 mg once a day

Perennial Allergic Rhinitis:
6 months to 5 years: 1.25 mg orally once a day in the evening
6 to 11 years: 2.5 mg orally once a day in the evening
12 years or older: 5 mg orally once a day in the evening; some patients may be adequately controlled on 2.5 mg once a day

Comments:
-The recommended doses in pediatric patients 6 months to 12 years should not be exceeded because the systemic exposure with 5 mg is about twice that of adults.

Uses: For the relief of symptoms associated with seasonal and perennial allergic rhinitis

Liver Dose Adjustments

No adjustment recommended.

Administrative Information

LactMed Record Number

702

Last Revision Date

20140116

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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