Cetirizine

For adults and adolescents aged 12 years and older, the standard recommended dose of cetirizine is 5 mg to 10 mg taken orally once daily.

• Standard Dose: 10 mg once daily is the most common dose for maximum symptom relief.
• Mild Symptoms: A 5 mg dose may be sufficient for patients with less severe symptoms or those who are more sensitive to the sedative effects of the medication.
• Maximum Dose: Do not exceed 10 mg in a 24-hour period unless specifically directed by a physician. Taking more than the recommended dose does not typically increase efficacy but significantly increases the risk of somnolence (drowsiness).

Cetirizine is approved for use in children as young as 6 months, but the dosage must be carefully calibrated based on age:

• Infants 6 months to 23 months: The typical dose is 2.5 mg (half a teaspoon of syrup) once daily. For infants 12-23 months, the dose may be increased to a maximum of 2.5 mg every 12 hours if needed.
• Children 2 to 5 years: The starting dose is 2.5 mg once daily. This can be increased to a maximum of 5 mg per day, given either as a single 5 mg dose or 2.5 mg every 12 hours.
• Children 6 to 11 years: The recommended dose is 5 mg or 10 mg once daily, depending on the severity of symptoms. Do not exceed 10 mg in 24 hours.

Renal Impairment

Because cetirizine is primarily cleared by the kidneys, patients with decreased kidney function require lower doses to prevent drug accumulation and toxicity:

• Mild Impairment (CrCl 50-79 mL/min): 5 mg once daily.
• Moderate Impairment (CrCl 30-49 mL/min): 5 mg every other day.
• Severe Impairment (CrCl <30 mL/min): Consultation with a specialist is required; doses are typically 5 mg twice weekly or avoided entirely.
• End-Stage Renal Disease/Hemodialysis: Generally contraindicated.

Hepatic Impairment

In patients with impaired liver function, the metabolism of cetirizine is not significantly affected, but the overall clearance may be reduced. A dose of 5 mg once daily is generally recommended for patients with significant hepatic impairment.

Elderly Patients

Patients aged 65 and older may have undiagnosed reductions in renal function. It is often recommended to start at 5 mg once daily and monitor for increased side effects, particularly sedation and confusion.

• Consistency: Cetirizine can be taken with or without food. Taking it with food may help if you experience stomach upset.
• Timing: While it is a 24-hour medication, some patients find that taking it in the evening is preferable if they experience mild drowsiness.
• Administration: Swallow tablets whole with a glass of water. For chewable tablets, chew thoroughly before swallowing. For orally disintegrating tablets, allow the tablet to dissolve on the tongue and then swallow.
• Storage: Store at room temperature (68°F to 77°F or 20°C to 25°C) in a dry place away from direct sunlight.

If you miss a dose, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not take two doses at once to make up for a missed one, as this increases the risk of side effects.

An overdose of cetirizine typically manifests as extreme somnolence. In children, an overdose may initially cause agitation or restlessness followed by extreme drowsiness.

• Signs: Severe dizziness, extreme sleepiness, or a rapid heart rate.
• Action: In the event of a suspected overdose, contact your local Poison Control Center or seek emergency medical attention immediately. There is no specific antidote for cetirizine; treatment is supportive and symptomatic.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or the frequency of use without medical guidance, especially when treating children or the elderly.

While cetirizine is generally well-tolerated, some individuals may experience side effects. The most frequently reported side effect is somnolence (drowsiness). Although marketed as a second-generation antihistamine, clinical trials showed that approximately 13.7% of patients taking 10 mg of cetirizine experienced drowsiness, compared to 6.3% of those taking a placebo.

Other common effects include:

• Fatigue: A general feeling of tiredness or lethargy that may persist throughout the day.
• Dry Mouth (Xerostomia): A decrease in saliva production, which can be managed by sipping water or using sugar-free lozenges.
• Dizziness: A feeling of lightheadedness or unsteadiness, particularly when moving quickly from a sitting to a standing position.

These effects occur in a smaller subset of the population but are still documented in clinical literature:

• Pharyngitis (Sore Throat): Irritation of the throat, sometimes accompanied by a dry cough.
• Abdominal Pain: Mild stomach discomfort or cramping.
• Epistaxis (Nosebleed): Particularly in patients using cetirizine for nasal allergies where the nasal mucosa may already be irritated.
• Nausea and Vomiting: More common in pediatric patients than in adults.

Rarely, patients may experience more unusual reactions:

• Paradoxical Excitation: Instead of drowsiness, some patients (especially children) may become hyperactive, restless, or experience insomnia.
• Tachycardia: An abnormally rapid heart rate or palpitations.
• Liver Enzyme Elevations: Transient increases in liver function tests (ALT/AST), which usually resolve after discontinuing the medication.
• Urinary Retention: Difficulty starting urination or fully emptying the bladder, primarily in men with enlarged prostates.

> Warning: Stop taking Cetirizine and call your doctor immediately or seek emergency care if you experience any of the following:

• Anaphylaxis: A severe allergic reaction characterized by hives, swelling of the face, lips, or tongue, difficulty breathing, and a sharp drop in blood pressure.
• Angioedema: Deep swelling under the skin, often around the eyes or mouth, which can be life-threatening if it affects the airway.
• Severe Visual Disturbances: Blurred vision or eye pain that does not resolve.
• Seizures: Though extremely rare, convulsions have been reported in some patients with pre-existing seizure disorders.
• Cholestasis: A condition where bile flow from the liver is blocked, resulting in yellowing of the skin or eyes (jaundice), dark urine, and intense itching.

Cetirizine is generally considered safe for long-term use when taken as directed. However, some patients report a phenomenon known as 'Cetirizine Withdrawal Pruritus'. Upon suddenly stopping the medication after months or years of daily use, some individuals experience intense, generalized itching (pruritus) that can last for several days to weeks. This is not an allergy to the drug itself but a rebound effect of the H1 receptors. Tapering the dose slowly under medical supervision can help prevent this.

No FDA black box warnings exist for Cetirizine. It is considered to have a high safety profile for the general population when used according to the label instructions.

Report any unusual symptoms or side effects to your healthcare provider. Monitoring your body's response during the first few days of treatment is essential to ensure the medication is both safe and effective for you.

Cetirizine is a highly effective medication, but it must be used with caution in specific circumstances. The most critical safety point is the potential for Central Nervous System (CNS) depression. While cetirizine is less likely to cause sedation than older antihistamines, it can still impair mental alertness and physical coordination. Patients should be aware of how they react to the medication before engaging in hazardous activities.

There are currently no FDA black box warnings for cetirizine. It does not carry the high-risk profile associated with medications that require such warnings, such as certain antidepressants or blood thinners.

• Allergic Reactions: While cetirizine treats allergies, it is possible to be allergic to the drug itself or its inactive ingredients (such as lactose or corn starch). If you develop a rash, hives, or swelling after taking it, discontinue use immediately.
• Renal Function: Because the kidneys are responsible for clearing the majority of the drug from the system, those with kidney disease are at a higher risk of toxicity. High levels of cetirizine in the blood can lead to severe lethargy and respiratory depression.
• Urinary Retention: Antihistamines can occasionally worsen symptoms of urinary obstruction. Patients with benign prostatic hyperplasia (BPH) or bladder neck obstruction should use cetirizine with caution.
• Seizure Disorders: There have been rare reports of cetirizine lowering the seizure threshold. Patients with a history of epilepsy should consult their neurologist before use.

For most healthy individuals taking cetirizine over-the-counter, routine lab monitoring is not required. However, for those with chronic conditions:

• Renal Function Tests: Periodic monitoring of Creatinine and Glomerular Filtration Rate (GFR) is recommended for elderly patients or those with known kidney issues.
• Liver Function: If long-term, high-dose therapy is used, occasional liver enzyme checks may be prudent, though liver injury is exceptionally rare.
• Allergy Skin Testing: Cetirizine will interfere with the results of allergy skin tests. You must stop taking the medication at least 3 to 4 days before undergoing any skin prick testing to ensure accurate results.

Exercise caution when driving a motor vehicle or operating heavy machinery until you are reasonably certain that cetirizine does not make you drowsy. Clinical studies show that at the 10 mg dose, a measurable percentage of the population experiences enough sedation to potentially impair reaction times.

Avoid the consumption of alcohol while taking cetirizine. Alcohol can significantly increase the sedative effects of the medication, leading to dangerous levels of drowsiness, impaired judgment, and loss of motor control. This additive effect is one of the most common causes of adverse events involving second-generation antihistamines.

For most users, cetirizine can be stopped abruptly without issue. However, as noted in the side effects section, long-term users (those taking it daily for >6 months) may experience rebound itching. If you have been on cetirizine long-term, consider reducing your dose to 5 mg for a week, then 2.5 mg for another week before stopping entirely.

> Important: Discuss all your medical conditions, including any history of kidney or liver disease, with your healthcare provider before starting Cetirizine.

There are no absolute contraindications for drug-drug combinations that result in fatal outcomes, but the following should be strictly avoided due to severe risk:

• Isocarboxazid / Tranylcypromine (MAOIs): While the interaction is more significant with first-generation antihistamines, taking cetirizine with Monoamine Oxidase Inhibitors can potentially lead to increased anticholinergic effects and blood pressure fluctuations.

• CNS Depressants (Opioids, Benzodiazepines, Barbiturates): Medications such as oxycodone, alprazolam (Xanax), or zolpidem (Ambien) have additive effects with cetirizine. Combining these can lead to profound sedation, respiratory depression, and impaired cognitive function.
• Theophylline: Some studies have shown that theophylline (used for asthma/COPD) can slightly decrease the clearance of cetirizine from the body, leading to higher blood levels and a greater risk of side effects.

• Anticholinergic Drugs: Medications used for overactive bladder (e.g., oxybutynin) or Parkinson's disease (e.g., benztropine) may have additive drying effects when taken with cetirizine, leading to severe dry mouth, constipation, and blurred vision.
• Other Antihistamines: Do not combine cetirizine with other H1 antagonists (like loratadine or diphenhydramine) unless directed by a doctor, as this increases the risk of toxicity without providing additional therapeutic benefit.

• Alcohol: As previously mentioned, alcohol is the most significant 'food' interaction. It enhances the CNS-depressant effects of cetirizine.
• Grapefruit Juice: Unlike many other drugs, cetirizine's metabolism is not significantly affected by grapefruit juice because it does not rely on the CYP3A4 enzyme system.
• High-Fat Meals: A high-fat meal can delay the time it takes for cetirizine to reach peak concentration (Tmax) by about 1.25 hours, but it does not change the overall effectiveness of the drug.

• Valerian / Kava / St. John's Wort: These supplements have sedative properties. When combined with cetirizine, they can cause excessive sleepiness and reduced mental clarity.
• Magnesium/Aluminum Antacids: While not a major interaction, taking large doses of antacids simultaneously with cetirizine may slightly alter the absorption rate of the medication.

• Allergy Skin Tests: Cetirizine prevents the 'wheal and flare' reaction to allergens. It must be discontinued 72-96 hours before testing to prevent false-negative results.

Mechanism of Interactions: Most cetirizine interactions are pharmacodynamic (the drugs have additive effects on the body) rather than pharmacokinetic (the drugs change how the other is metabolized). Because cetirizine bypasses the liver's CYP450 system, it is much safer than many other medications in terms of metabolic interference.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A complete medication reconciliation is the best way to prevent dangerous interactions.

Cetirizine must NEVER be used in the following circumstances:

1. 1Hypersensitivity to Cetirizine: If you have had a previous allergic reaction to cetirizine, you must not take it again. Reactions can range from mild rashes to life-threatening anaphylaxis.
2. 2Hypersensitivity to Hydroxyzine: Cetirizine is the primary metabolite of hydroxyzine (Atarax). Therefore, anyone with a known allergy to hydroxyzine will almost certainly be allergic to cetirizine due to their nearly identical chemical structures.
3. 3Hypersensitivity to Levocetirizine: Levocetirizine (Xyzal) is the active enantiomer of cetirizine. Cross-reactivity is guaranteed.
4. 4End-Stage Renal Disease (ESRD): Patients with a Creatinine Clearance (CrCl) of less than 10 mL/min or those undergoing hemodialysis should not use cetirizine. The drug cannot be cleared from the system, leading to rapid accumulation and dangerous CNS depression.

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

• Severe Hepatic Impairment: While not an absolute contraindication, the risk of reduced clearance requires significant dose adjustment.
• Prostatic Hypertrophy (Enlarged Prostate): The mild anticholinergic potential of cetirizine may exacerbate urinary retention.
• Angle-Closure Glaucoma: Antihistamines can occasionally increase intraocular pressure, which is dangerous for individuals with this specific type of glaucoma.

Patients should be aware of cross-sensitivity within the piperazine derivative class of antihistamines. If you have had an adverse reaction to medications like meclizine (used for vertigo) or cyclizine, you should inform your doctor before starting cetirizine, as these drugs share similar chemical backbones.

> Important: Your healthcare provider will evaluate your complete medical history, including kidney function and previous drug allergies, before prescribing Cetirizine or recommending it for OTC use.

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

• First Trimester: Large-scale observational studies have not shown an increased risk of major malformations when cetirizine is used during the first trimester.
• Clinical Recommendation: While generally considered one of the safer antihistamines during pregnancy, it should only be used if clearly needed. Most obstetricians prefer the use of cetirizine or loratadine over older antihistamines like diphenhydramine due to the lower risk of maternal sedation.

Cetirizine is excreted in human breast milk. Studies estimate that a nursing infant receives approximately 1% to 3% of the maternal weight-adjusted dose.

• Risks: While this amount is small, antihistamines can potentially cause irritability or drowsiness in the nursing infant.
• Milk Supply: High doses of antihistamines can occasionally decrease milk production by inhibiting the effects of histamine on prolactin secretion.
• Recommendation: Short-term or occasional use is likely safe, but long-term use should be discussed with a pediatrician.

Cetirizine is approved for pediatric use in children as young as 6 months. It is widely considered safe and effective for treating allergic rhinitis and hives in children.

• Growth and Development: There is no evidence that long-term use of cetirizine affects growth or cognitive development in children.
• Caution: The most common side effect in children is headache and stomach upset, though paradoxical excitability (nervousness/insomnia) occurs more frequently in children than in adults.

In patients aged 65 and older, the half-life of cetirizine is prolonged by approximately 50%, and the clearance is reduced by 40%.

• Fall Risk: Due to the increased risk of sedation and dizziness, elderly patients are at a higher risk of falls while taking cetirizine.
• Dosing: Clinical guidelines suggest starting at 5 mg once daily for all geriatric patients to account for the natural age-related decline in renal function.

As the kidneys are the primary route of elimination, dosing must be adjusted based on the patient's Creatinine Clearance (CrCl):

• CrCl 30-49 mL/min: 5 mg once daily.
• CrCl 11-29 mL/min: 5 mg every other day.
• CrCl <10 mL/min: Contraindicated.

In patients with chronic liver disease, the clearance of cetirizine is reduced. A maximum dose of 5 mg once daily is typically recommended for those with significant hepatic dysfunction (Child-Pugh Class B or C).

> Important: Special populations require individualized medical assessment. Never start a new medication for a child, elderly person, or during pregnancy without consulting a healthcare professional.

Cetirizine is a highly potent and selective antagonist of the peripheral H1 receptors. Its primary mechanism involves competing with free histamine for binding sites on effector cells. Unlike first-generation antihistamines, cetirizine has a very low affinity for the H1 receptors in the brain.

Furthermore, cetirizine has been shown to have anti-inflammatory properties beyond simple H1 antagonism. At therapeutic doses, it inhibits the late-phase recruitment of inflammatory cells, particularly eosinophils, to the site of an allergic reaction. It also reduces the expression of adhesion molecules like ICAM-1, which are necessary for inflammatory cells to migrate into tissues. This dual action makes it particularly effective for chronic allergic conditions.

• Onset of Action: Symptom relief typically begins within 20 to 60 minutes after oral administration.
• Duration: The effects persist for at least 24 hours, allowing for convenient once-daily dosing.
• Tolerance: There is no evidence of tachyphylaxis (developing a tolerance) to cetirizine; it remains effective even with daily long-term use.

| Parameter | Value |

|---|---|

| Bioavailability | ~70% |

| Protein Binding | 93% |

| Half-life (Adults) | 8.3 hours |

| Half-life (Children) | 6-7 hours |

| Tmax (Time to peak) | 1.0 hour |

| Metabolism | Minimal (Non-CYP) |

| Excretion | Renal 70%, Fecal 10% |

• Molecular Formula: C21H25ClN2O3
• Molecular Weight: 388.89 g/mol
• Solubility: Highly soluble in water; practically insoluble in acetone and methylene chloride.
• Structure: It is a racemic compound, consisting of a 1:1 mixture of (R) and (S) enantiomers. The (R)-enantiomer (levocetirizine) is the more active component.

Cetirizine is classified as a Second-Generation Antihistamine and a Piperazine Derivative. It is chemically related to hydroxyzine but lacks the significant CNS penetration and anticholinergic activity of its parent compound. Related medications in this class include levocetirizine, loratadine, and fexofenadine.