Levocetirizine Dihydrochloride

For adults and adolescents 12 years of age and older, the standard recommended dose of Levocetirizine Dihydrochloride is 5 mg once daily. Clinical data suggests that taking the medication in the evening is most effective for many patients, as it ensures peak levels are present the following morning when allergy symptoms are often most severe, and it allows any potential somnolence (drowsiness) to occur during sleep.

For patients with Chronic Idiopathic Urticaria, the dose remains 5 mg once daily. It is important not to exceed this dose, as clinical trials have shown that higher doses do not necessarily provide additional relief but do significantly increase the risk of side effects.

Pediatric dosing is strictly based on age to ensure safety and efficacy:

• Children 6 to 11 years of age: The recommended dose is 2.5 mg (half of a 5 mg tablet or 5 mL of oral solution) once daily in the evening.
• Children 6 months to 5 years of age: The recommended dose is 1.25 mg (2.5 mL of oral solution) once daily in the evening.
• Infants under 6 months: Safety and effectiveness have not been established; use is generally not recommended in this age group.

Because the kidneys are the primary route for removing this drug from the body, dosage adjustments are mandatory for patients with reduced kidney function.

Renal Impairment

• Mild (CrCl 50–80 mL/min): 2.5 mg once daily.
• Moderate (CrCl 30–50 mL/min): 2.5 mg once every other day.
• Severe (CrCl 10–30 mL/min): 2.5 mg twice weekly (once every 3 to 4 days).
• End-Stage Renal Disease (CrCl < 10 mL/min): Use is contraindicated (strictly prohibited).

Hepatic Impairment

In patients with purely hepatic (liver) impairment, no dosage adjustment is typically required because the liver plays a minimal role in metabolizing the drug. However, if a patient has both liver and kidney impairment, the renal guidelines must be followed.

Elderly Patients

Selection of the dose for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

• Administration: Tablets should be swallowed whole with a glass of water. They can be taken with or without food. If using the oral solution, use a calibrated measuring device (not a household spoon) to ensure the correct dose.
• Timing: Consistency is key. Take the dose at the same time each evening.
• Storage: Store the medication at room temperature (20°C to 25°C or 68°F to 77°F) in a dry place away from direct sunlight and moisture.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up, as this increases the risk of excessive sedation.

Symptoms of overdose in adults may include extreme drowsiness. In children, an overdose may initially cause agitation and restlessness, followed by drowsiness. In the event of a suspected overdose, contact your local Poison Control Center or seek emergency medical attention immediately. Treatment is generally supportive, as there is no specific antidote for levocetirizine, and it is not effectively removed by dialysis.

> Important: Follow your healthcare provider's dosing instructions precisely. Do not adjust your dose or stop taking the medication without medical guidance, as your symptoms may return.

While Levocetirizine Dihydrochloride is generally well-tolerated, some patients may experience side effects. The most commonly reported side effect is somnolence (drowsiness or sleepiness). Although it is a second-generation antihistamine, approximately 6% of adults in clinical trials reported some level of tiredness. This effect is dose-dependent and varies by individual sensitivity.

Other common side effects include:

• Xerostomia (Dry Mouth): A feeling of dryness in the mouth or throat, which can sometimes be managed by sipping water or using sugarless lozenges.
• Fatigue: A general sense of tiredness or lack of energy.
• Pharyngitis (Sore Throat): Mild irritation or inflammation of the throat was noted in several pediatric and adult trials.

These effects occur in a smaller percentage of the population but are well-documented:

• Nasopharyngitis: Symptoms similar to a common cold, including nasal congestion.
• Pyrexia (Fever): More commonly observed in pediatric populations than in adults.
• Cough: A persistent dry cough has been reported in children taking the oral solution.
• Epistaxis (Nosebleed): Occasional nosebleeds, particularly in children treated for allergic rhinitis.

Rarely, patients may experience:

• Dysuria (Painful Urination): Difficulty or pain when passing urine.
• Visual Disturbances: Blurred vision or changes in visual acuity.
• Palpitations: A sensation that the heart is racing, fluttering, or skipping a beat.
• Weight Gain: While less common than with some older antihistamines, minor weight changes have been reported in long-term studies.

In rare instances, Levocetirizine Dihydrochloride can cause severe reactions. You should contact emergency services or your doctor immediately if you experience:

• Anaphylaxis or Severe Allergic Reaction: Symptoms include swelling of the face, lips, tongue, or throat; difficulty breathing or swallowing; severe rash or hives; and feeling faint.
• Urinary Retention: An inability to empty the bladder completely. This is a medical emergency and requires immediate intervention.
• Severe CNS Depression: Extreme lethargy or inability to wake up.
• Psychiatric Symptoms: While rare, post-marketing reports have included instances of suicidal ideation, hallucinations, or severe depression. If your mood changes significantly, seek help immediately.

> Warning: Stop taking Levocetirizine Dihydrochloride and call your doctor immediately if you experience any signs of a serious allergic reaction or inability to urinate.

For most people, levocetirizine is safe for long-term use when taken as directed. However, some patients may develop a 'rebound' effect if the medication is stopped abruptly after years of use. This is known as discontinuation pruritus (intense itching after stopping the drug). This itching can be severe and may last for several days or weeks before resolving. It is not an allergic reaction to the drug's absence but rather a physiological response of the H1 receptors. If you have been taking levocetirizine for a long duration, discuss a tapering schedule with your doctor.

There are currently no FDA black box warnings for Levocetirizine Dihydrochloride. It is considered to have a high safety profile when used according to the established dosing guidelines and in the absence of severe renal impairment.

Report any unusual symptoms or side effects to your healthcare provider. Monitoring your body's response is essential for safe long-term allergy management.

Levocetirizine Dihydrochloride, while effective, requires careful use under certain conditions. The most critical safety point is the risk of Central Nervous System (CNS) depression. Patients must be aware that even though it is marketed as a non-drowsy antihistamine, it can cause significant somnolence in some individuals. This risk is compounded when the drug is taken with other substances that also depress the CNS, such as alcohol or sedatives.

No FDA black box warnings for Levocetirizine Dihydrochloride. It is generally regarded as safe for the general population when renal function is taken into account.

Allergic Reactions / Anaphylaxis Risk

Patients with a known hypersensitivity to levocetirizine, cetirizine (Zyrtec), or hydroxyzine (Atarax) should never use this medication. Cross-sensitivity is common among these chemically related compounds. A severe reaction can lead to anaphylaxis, which is life-threatening.

Urinary Retention

Levocetirizine should be used with caution in patients with pre-disposing factors for urinary retention, such as prostatic hypertrophy (enlarged prostate) or spinal cord lesions. Antihistamines can decrease bladder contractility, making it difficult to urinate. If you experience difficulty starting a stream or feel your bladder is not emptying, consult your doctor immediately.

Renal Function

As the kidneys are responsible for clearing over 80% of the drug, any degree of renal impairment significantly increases the concentration of the drug in the blood. This increases the risk of toxic effects. Regular monitoring of Creatinine Clearance (CrCl) is necessary for patients with known kidney disease.

For most healthy patients, routine lab work specifically for levocetirizine is not required. However, for specific groups:

• Renal Function Tests: Periodic monitoring of serum creatinine and GFR is recommended for elderly patients and those with pre-existing kidney conditions.
• Symptom Tracking: Patients should monitor the efficacy of the drug and report if symptoms of allergic rhinitis do not improve or if hives worsen.

Patients are cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination, such as operating machinery or driving a motor vehicle, until they know how Levocetirizine Dihydrochloride affects them. In clinical trials, somnolence was reported in a significant minority of patients, and its effects can be unpredictable.

Concurrent use of Levocetirizine Dihydrochloride with alcohol or other CNS depressants should be avoided. Alcohol can potentiate (increase) the sedative effects of the antihistamine, leading to severe impairment of judgment and physical coordination.

There is no evidence of physical addiction to levocetirizine. However, as mentioned in the side effects section, some patients experience intense itching (pruritus) upon stopping the medication after long-term use. If you plan to stop the medication after several months of daily use, your doctor may suggest gradually reducing the frequency of the dose rather than stopping 'cold turkey.'

> Important: Discuss all your medical conditions, especially kidney disease or prostate issues, with your healthcare provider before starting Levocetirizine Dihydrochloride.

There are few absolute contraindications for drug combinations with levocetirizine; however, it must NEVER be used in patients with End-Stage Renal Disease (ESRD) who are on hemodialysis. In these patients, the drug cannot be cleared, leading to dangerous accumulation and toxicity.

CNS Depressants

Drugs such as benzodiazepines (e.g., diazepam, lorazepam), opioids (e.g., oxycodone, hydrocodone), and certain sleep medications (e.g., zolpidem) can have an additive effect with levocetirizine. This means the combination can cause extreme drowsiness, slowed breathing, and impaired motor skills.

• Mechanism: Pharmacodynamic synergism of CNS depression.
• Management: Avoid combination if possible; if necessary, use the lowest effective dose and monitor for respiratory depression.

Ritonavir

Ritonavir, an antiviral used in the treatment of HIV, may increase the plasma levels of certain antihistamines. While the specific interaction with levocetirizine is less pronounced than with cetirizine, caution is advised.

• Mechanism: Potential inhibition of transport proteins like P-glycoprotein.
• Management: Monitor for increased side effects like dry mouth and drowsiness.

Theophylline

A small decrease (about 16%) in the clearance of levocetirizine has been observed when taken with theophylline (a bronchodilator). While not typically clinically significant for most, it may increase the half-life of the antihistamine slightly.

• Management: No specific dose adjustment is usually required, but patients should be aware of a possible increase in duration of side effects.

Alcohol

As noted, alcohol is the most significant 'food' interaction. Even small amounts of alcohol can significantly increase the drowsiness caused by levocetirizine.

High-Fat Meals

Taking levocetirizine with a high-fat meal does not change the total amount of drug your body absorbs, but it does slow down how fast it gets into your system. If you need immediate relief from a sudden allergy flare-up, taking it on an empty stomach may result in slightly faster onset.

Sedating Herbs

Supplements such as Valerian root, Kava, and Melatonin may increase the sedative effects of levocetirizine.

• Clinical Consequence: Increased risk of daytime sleepiness and falls, especially in the elderly.
• Management: Use caution when combining these supplements with your allergy medication.

St. John's Wort

While St. John's Wort primarily affects drugs metabolized by the CYP3A4 enzyme (which levocetirizine does not rely on heavily), it can affect various transport proteins. Patients should inform their doctor if they use this herbal supplement.

Levocetirizine Dihydrochloride can interfere with the results of allergy skin tests. Because the drug prevents the skin from reacting to allergens, it can cause a 'false negative' result.

• Management: Patients should typically stop taking levocetirizine at least 3 to 5 days before undergoing skin prick testing. Always inform your allergist of all medications you are taking.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter cold and flu medicines which may also contain antihistamines.

There are specific circumstances where Levocetirizine Dihydrochloride must never be used due to the high risk of harm:

1. 1Hypersensitivity: Any patient with a known allergy to levocetirizine, cetirizine, or the parent compound hydroxyzine. An allergic reaction to one of these usually indicates an allergy to all of them. The mechanism is an IgE-mediated immune response to the piperazine derivative structure of the molecule.
2. 2End-Stage Renal Disease (ESRD): Patients with a Creatinine Clearance (CrCl) of less than 10 mL/min must not take this medication. Because the drug is almost entirely cleared by the kidneys, ESRD leads to toxic levels in the blood, which can cause severe CNS depression and cardiac arrhythmias.
3. 3Hemodialysis: Patients undergoing hemodialysis are contraindicated for the same reasons as those with ESRD; the dialysis process does not efficiently remove levocetirizine from the bloodstream.
4. 4Pediatric Patients with Renal Impairment: Children aged 6 months to 11 years who have any degree of impaired kidney function should not use levocetirizine, as safe dosing for this specific sub-group has not been established.

These are conditions where the drug should be used only if the benefits outweigh the risks, and under close medical supervision:

• Prostatic Hyperplasia (Enlarged Prostate): The anticholinergic-like effects (though weak) can trigger acute urinary retention.
• Bladder Neck Obstruction: Similar to prostate issues, any physical obstruction in the urinary tract increases the risk of the drug causing an inability to urinate.
• Pregnancy: While not strictly contraindicated, it should only be used if clearly needed (see Special Populations).

Patients should be aware of cross-sensitivity with other piperazine derivatives. If you have had a severe rash, hives, or breathing trouble after taking Zyrtec (cetirizine) or Vistaril/Atarax (hydroxyzine), you are highly likely to have the same reaction to Levocetirizine Dihydrochloride. Always provide a full list of drug allergies to your pharmacist.

> Important: Your healthcare provider will evaluate your complete medical history, including your kidney function and past reactions to antihistamines, before prescribing Levocetirizine Dihydrochloride.

Levocetirizine Dihydrochloride was previously classified as Pregnancy Category B. This means that animal reproduction studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

• Trimester-Specific Risks: There is no evidence of teratogenicity (birth defects) in animal studies at doses many times higher than the human dose. However, most healthcare providers recommend using antihistamines during pregnancy only when the symptoms are significantly affecting the mother's quality of life.
• Recommendation: Consult your OB/GYN before use. Often, older antihistamines with more long-term human data (like chlorpheniramine) may be preferred as first-line options in pregnancy.

Levocetirizine is expected to be excreted in human milk, as cetirizine is known to pass into breast milk.

• Effects on Infant: Potential effects include irritability or unusual sleepiness in the nursing infant.
• Milk Supply: Large doses of antihistamines may potentially decrease milk production in some women.
• Recommendation: Use with caution. If use is necessary, the lowest dose should be taken, and the infant should be monitored for signs of drowsiness.

Levocetirizine is FDA-approved for pediatric use down to 6 months of age.

• 6 months to 5 years: Approved for perennial allergic rhinitis and chronic urticaria. Dose is 1.25 mg daily.
• 6 years and older: Approved for seasonal allergic rhinitis.
• Safety: In pediatric trials, the most common side effects were pyrexia (fever), cough, and somnolence. It is vital to use the oral solution for precise dosing in young children.

Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, because elderly patients are more likely to have decreased renal function, dose selection should be cautious.

• Fall Risk: Increased sensitivity to the sedative effects can increase the risk of falls and hip fractures in the elderly.
• Renal Clearance: CrCl should be calculated before starting the drug in any elderly patient.

As discussed, the dose must be adjusted based on the severity of kidney disease. In patients with moderate to severe impairment, the dosing interval is increased (e.g., taking the pill every 3 days instead of every day) to prevent the drug from building up to dangerous levels.

No dosage adjustment is required for patients with liver disease alone. The drug is primarily excreted unchanged by the kidneys, so the liver's metabolic capacity does not significantly affect how the drug is cleared.

> Important: Special populations, particularly the elderly and those with kidney disease, require individualized medical assessment and frequent monitoring to ensure the medication remains safe and effective.

Levocetirizine Dihydrochloride is the (R)-enantiomer of cetirizine. It is a potent and selective peripheral H1-receptor antagonist. Its primary action is to compete with endogenous (naturally occurring) histamine for H1-receptor sites on the effector cells.

At the molecular level, levocetirizine is considered an inverse agonist. This means it does not just block the receptor but actually stabilizes it in its inactive form, further reducing the 'leakage' of inflammatory signals even when histamine levels are low. It has a high affinity for the H1 receptor—approximately two times higher than that of cetirizine. Because it dissociates (detaches) from the receptor very slowly, it provides a long duration of action, allowing for once-daily dosing.

• Onset of Action: Patients typically begin to feel relief within 1 hour of taking the dose.
• Duration: The H1-receptor occupancy remains high for 24 hours, providing a full day of symptom control.
• Selectivity: It has very low affinity for other receptors, such as muscarinic, cholinergic, or alpha-adrenergic receptors, which is why it has fewer 'drying' side effects (like constipation) compared to first-generation antihistamines.

| Parameter | Value |

|---|---|

| Bioavailability | >70% (Rapidly absorbed) |

| Protein Binding | 91% - 92% |

| Half-life | 8 - 9 hours (Adults) |

| Tmax | 0.9 hours |

| Metabolism | Minimal (<14%), non-CYP dependent |

| Excretion | Renal 85.4%, Fecal 12.9% |

• Molecular Formula: C21H25ClN2O3·2HCl
• Molecular Weight: 461.81 g/mol
• Solubility: Highly soluble in water and freely soluble in methanol.
• Structure: It is a carboxylic acid derivative and a member of the piperazine class of antihistamines.

Levocetirizine belongs to the Second-Generation Antihistamine class. It is specifically a 'systemic antihistamine' used for allergic conditions. It is closely related to cetirizine (Zyrtec) and hydroxyzine (Atarax). Compared to first-generation drugs like diphenhydramine (Benadryl), it is significantly less sedating and has a longer half-life.