Levocetirizine

Usage

Levocetirizine is prescribed for the symptomatic relief of allergic conditions such as:

• Seasonal allergic rhinitis (hay fever): Nasal congestion, runny nose, sneezing, itchy eyes, and watery eyes caused by pollen and other allergens.
• Perennial allergic rhinitis: Similar symptoms to hay fever but occurring year-round due to allergens like dust mites, pet dander, and mold.
• Chronic idiopathic urticaria (hives): Itchy, raised welts on the skin appearing without a known cause.

Pharmacological Classification: Levocetirizine is a second-generation antihistamine.

Mechanism of Action: It acts as a selective inverse agonist at the histamine H1 receptor. By binding to and stabilizing the inactive state of this receptor, it inhibits the actions of histamine, reducing allergic symptoms.

Alternate Names

Levocetirizine Dihydrochloride is the chemical name. Xyzal is a popular brand name. Other brands include Levrix.

How It Works

Pharmacodynamics: Levocetirizine binds preferentially to the H1 receptor, leading to decreased vascular permeability, reduced itching and edema, and suppression of other histamine-mediated effects.

Pharmacokinetics:

• Absorption: Well absorbed orally, with peak plasma concentration reached in about 0.9 hours. Food intake does not affect the extent of absorption but may slightly delay it.
• Metabolism: Minimally metabolized in the liver.
• Elimination: Primarily excreted unchanged in the urine, with a half-life of approximately 7.9 hours in adults. Creatinine clearance significantly impacts elimination.

Mode of Action: Levocetirizine acts as an inverse agonist at the peripheral H1 receptors. This is distinct from a competitive antagonist, as it not only blocks histamine binding but also shifts the receptor towards its inactive state, further suppressing constitutive activity.

Receptor binding: Selectively binds to H1 receptors.

Enzyme inhibition/neurotransmitter modulation: Does not significantly inhibit CYP450 enzymes or directly modulate neurotransmitters other than by its action on H1 receptors.

Elimination pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults: 5 mg once daily, preferably in the evening. Some patients may respond to 2.5 mg daily.

Children:

• 6 months to 5 years: 1.25 mg once daily in the evening (oral solution preferred).
• 6 to 11 years: 2.5 mg once daily in the evening.
• 12 years and older: 5 mg once daily in the evening.

Special Cases:

• Elderly Patients: Dose adjustment may be needed in elderly patients with moderate to severe renal impairment. Monitor renal function.
• Patients with Renal Impairment: Dosage adjustments are crucial (see below).
• Patients with Hepatic Dysfunction: No dose adjustment is typically required. However, use with caution in patients with both hepatic and renal impairment.
• Patients with Comorbid Conditions: Use with caution in patients with conditions that might predispose them to adverse effects, such as urinary retention (e.g., prostatic hyperplasia), epilepsy, or other seizure disorders.

Clinical Use Cases

Levocetirizine’s usage is primarily limited to allergic rhinitis and urticaria. It doesn’t have specific dosing recommendations for clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Other medications are typically employed in these contexts.

Dosage Adjustments

• Renal Impairment (Adults):

  • Creatinine clearance (CrCl) 50-80 mL/min: 2.5 mg once daily.
  • CrCl 30-50 mL/min: 2.5 mg every other day.
  • CrCl 10-30 mL/min: 2.5 mg twice a week (every 3-4 days).
  • CrCl <10 mL/min or hemodialysis: Contraindicated.

• Renal Impairment (Children 6 months to 11 years): Contraindicated.

• Pediatric Dosing: Adjust based on weight and age as described above.

Side Effects

Common Side Effects:

• Somnolence (drowsiness)
• Fatigue
• Dry mouth
• Headache
• Pharyngitis

Rare but Serious Side Effects:

• Hypersensitivity reactions (anaphylaxis, angioedema)
• Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome)
• Seizures
• Hepatic dysfunction
• Thrombocytopenia

Long-Term Effects:

Limited data is available on specific long-term adverse effects. Regular monitoring for any emerging issues is recommended with prolonged use.

Adverse Drug Reactions (ADR):

Any signs of hypersensitivity or severe cutaneous reactions, neurologic events like seizures, or signs of hepatotoxicity should prompt immediate discontinuation and medical attention.

Contraindications

• Hypersensitivity to levocetirizine or cetirizine.
• End-stage renal disease (CrCl <10 mL/min) or patients on hemodialysis.
• Children aged 6 months to 11 years with renal impairment.

Drug Interactions

• CNS Depressants: Alcohol, sedatives, hypnotics, opioids can enhance the sedative effects of levocetirizine.
• Theophylline: May decrease the clearance of levocetirizine, requiring dose adjustments.
• Ritonavir: May increase levocetirizine exposure.
• CYP450 interactions: Levocetirizine has minimal CYP450 metabolism, reducing the potential for interactions. However, drugs impacting renal clearance might indirectly alter levocetirizine levels.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (animal studies show no risk, but human studies are limited). Use only if clearly needed.
• Fetal risks: Limited data suggests low risk.
• Breastfeeding: Small amounts may be excreted in breast milk. Monitor infants for drowsiness. Larger doses or prolonged use could decrease milk supply, especially if combined with sympathomimetics like pseudoephedrine. Consider alternative medications if necessary.

Drug Profile Summary

• Mechanism of Action: Selective H1 receptor inverse agonist.
• Side Effects: Drowsiness, fatigue, dry mouth, headache. Rarely: hypersensitivity reactions, seizures.
• Contraindications: Hypersensitivity, end-stage renal disease, renal impairment in children (6 months - 11 years).
• Drug Interactions: CNS depressants, theophylline, ritonavir.
• Pregnancy & Breastfeeding: Use cautiously if benefits outweigh risks.
• Dosage: Adults: 5 mg daily. Children: 1.25-5 mg daily based on age. Adjust for renal impairment.
• Monitoring Parameters: Renal function (especially in elderly and those with renal impairment).

Popular Combinations

Levocetirizine is sometimes combined with Montelukast, particularly for allergic rhinitis. Montelukast, a leukotriene receptor antagonist, works via a different mechanism and can provide additive benefits in managing allergic symptoms.

Precautions

• General Precautions: Evaluate renal function, particularly in the elderly and those with comorbidities. Pre-screen for hypersensitivity.
• Specific Populations: See sections above on Dosage (special cases) and Pregnancy and Breastfeeding.
• Lifestyle Considerations: Advise patients against operating machinery or driving if experiencing drowsiness. Alcohol may potentiate sedative effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Levocetirizine?

A: Adults and children 12 years and older: 5 mg once daily, usually in the evening. Children 6 to 11 years: 2.5 mg once daily. Children 6 months to 5 years: 1.25 mg once daily. Adjust dosage for renal impairment.

Q2: Can I take Levocetirizine with alcohol?

A: Alcohol can enhance the sedative effects of Levocetirizine. Concomitant use should be avoided or minimized.

Q3: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember. If it’s almost time for the next dose, skip the missed dose and return to your regular schedule. Do not double the dose.

Q4: Is Levocetirizine safe during pregnancy?

A: Levocetirizine is a pregnancy category B drug. Animal studies show no risk, but human data are limited. It should be used during pregnancy only if clearly needed and after careful risk-benefit assessment with the patient.

Q5: Can I breastfeed while taking Levocetirizine?

A: Levocetirizine is present in breast milk. Caution is advised, and monitoring infants for drowsiness is recommended. Larger doses or prolonged use might decrease milk supply. Consider the risks and benefits with the patient.

Q6: How long does it take for Levocetirizine to work?

A: The onset of action typically occurs within 1 hour, with effects lasting for at least 24 hours.

Q7: What are the serious side effects of Levocetirizine I should be aware of?

A: Rare but serious side effects include hypersensitivity reactions (anaphylaxis, angioedema), severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome), seizures, and hepatic dysfunction.

Q8: Does Levocetirizine interact with other medications?

A: Yes, Levocetirizine can interact with CNS depressants (e.g., alcohol, sedatives), theophylline, and ritonavir. Inform patients to disclose all medications and supplements they are taking.

Q9: Can I use Levocetirizine if I have kidney problems?

A: Dosage adjustments are necessary for patients with renal impairment. Levocetirizine is contraindicated in patients with end-stage renal disease or undergoing hemodialysis. Children with renal impairment should also avoid the drug.

Q10: What is the difference between Levocetirizine and Cetirizine?

A: Levocetirizine is the active R-enantiomer of cetirizine. It is considered more potent and less sedating than cetirizine, although both are effective antihistamines.