ACTION AND MECHANISM- [ANTIALLERGIC], [HISTAMINERGIC ANTAGONIST (H-1)]. Cetirizine is a long-acting piperazine derivative that competitively and reversibly blocks H1 receptors, decreasing the systemic effects of histamine. It causes vasoconstriction and decreased vascular permeability, reducing the redness and edema associated with allergies. It partially mitigates symptoms associated with allergic processes such as eye redness or nasal congestion. It also produces a mild bronchodilator effect and a reduction in skin itching. Cetirizine is the polar metabolite of hydroxyzine, a sedating piperazine antihistamine. However, its greater polarity compared to hydroxyzine means that it barely crosses the blood-brain barrier and causes sedation to a much lesser extent than other first-generation antihistamines, although more than piperidine derivatives. Its anticholinergic effects are also very insignificant, due to greater selectivity for H1 receptors. It lacks the cardiac effects of some second-generation antihistamines. SPECIAL WARNINGS - Due to the antiallergic effects of this medicine, it could give false negatives in skin tests for hypersensitivity to antigenic extracts. It is recommended to stop taking this medicine at least 72 hours before the test. ELDERLY Patients > 65 years of age have observed a reduction in the elimination of cetirizine, probably due to decreased renal function, rather than age itself. It does not seem necessary to adjust the dosage in these patients if renal function is normal. If function is reduced, the dosage should be adjusted similarly to those for patients with renal impairment (see Dosage under Renal Impairment). Furthermore, it should be taken into account that the elderly may be more sensitive to the adverse effects of antihistamines, such as dizziness, sedation, confusion, hypotension, and hyperexcitability. Although cetirizine does not usually cause intense drowsiness, and its anticholinergic effects are less than other antihistamines, it is advisable to use it with caution. If persistent or severe side effects occur, it may be advisable to discontinue treatment. PATIENT ADVICE - In very rare cases, it may cause drowsiness; therefore, it is recommended to be cautious when driving and not to combine it with drugs or other sedative substances such as alcohol. It is advisable to administer in a single dose. If adverse reactions occur or in young children, it is recommended to split the dose. It is advisable not to expose yourself to the sun during treatment. CONTRAINDICATIONS - Hypersensitivity to any component of the medication. There may be cross-reactions with other antihistamines, therefore the use of any H1 antihistamine is not recommended in patients who have presented hypersensitivity to any compound in this group.- [PORPHYRIA]. H1 antihistamines have been associated with the appearance of porphyric attacks, therefore they are not considered safe in these patients.- Severe renal impairment (CLcr < 10 ml/minute). The safety and efficacy of cetirizine have not been evaluated in patients with severe or severe renal impairment. EFFECTS ON DRIVING Cetirizine does not usually cause drowsiness as frequently as first-generation antihistamines, but its occurrence cannot be ruled out. Therefore, extreme caution is recommended when driving or operating dangerous machinery until there is reasonable certainty that the drug treatment does not adversely affect them. PREGNANCY FDA Category B. Safety in animals: In studies conducted with mice, rats and rabbits, using doses 40, 180 and 220 times higher than human therapeutic doses, no teratogenic effects have been recorded. Safety in humans: There are no adequate and well-controlled studies in humans. There are reports of a possible association between the use of antihistamines in general during the last 2 weeks of pregnancy and an increased risk of retrolental fibroplasia in premature children. The use of this medicine is only accepted in the absence of safer therapeutic alternatives. PHARMACOKINETICS Oral route: - Absorption: After oral administration, cetirizine is rapidly absorbed, reaching Cmax in one hour. Its bioavailability is approximately 70%. Its effects are longer-lasting than those of other first-generation antihistamines, reaching up to 24 hours. Food: When cetirizine is administered with food, absorption may be delayed, with increases in Tmax of 1.7 hours, but the amount absorbed is not significantly modified. - Distribution: Cetirizine is highly bound to plasma proteins (93%). Cetirizine does not appear to cross the placental barrier significantly, but it has been detected in milk. - Metabolism: It is partially metabolized in the liver through oxidation and O-dealkylation reactions via cytochrome P450. The metabolites formed are inactive. - Elimination: Cetirizine is mainly excreted by kidney elimination (90%), mainly unchanged, although occasionally up to 50% of the dose may be eliminated as metabolites. Only a small amount is excreted in the feces. Its elimination half-life in adults is about 6 hours.Pharmacokinetics in special situations:- Renal impairment: In patients with renal impairment, the clearance of cetirizine is decreased, so that in patients with severe renal impairment (CLcr less than 10 ml/minute) undergoing hemodialysis, the half-life may reach up to 20 hours, with a clearance of 0.3 ml/minute/kg.- Children: Cetirizine is eliminated more rapidly in children, with plasma half-life values of 6 hours for children aged 6-12 years, 5 hours for children aged 2-6 years, and 3 hours for children under 2 years.- Elderly: A decrease in clearance has been observed, probably related to a physiological reduction in renal function. The elimination half-life is approximately 12 hours, and the clearance is 0.55 ml/minute/kg. INDICATIONS - Treatment of nasal and ocular symptoms of [SEASONAL ALLERGIC RHINITIS] and [PERENNIAL ALLERGIC RHINITIS]. INTERACTIONS Cetirizine does not exert very appreciable sedative effects, but extreme caution is recommended when administering sedative drugs or alcohol, since the central depressant action may be potentiated. Cetirizine may potentiate the photosensitizing effects of other active ingredients, leading to photosensitivity reactions. In addition, drug interactions have been reported with the following active ingredients: - Oral anticoagulants (acenocoumarol). The concomitant administration of acenocoumarol and cetirizine has led to some cases of potentiation of the anticoagulant effect, probably due to a displacement of protein binding. This interaction appears to be especially important in patients with renal failure, while in cases of normal renal function it does not appear to be very significant. However, it is recommended to monitor the patient and readjust the anticoagulant dose if necessary. - Theophylline. After administering a dose of 400 mg of theophylline, a 16% decrease in the clearance of cetirizine was observed. Patient monitoring may be necessary. BREASTFEEDING Cetirizine is excreted in breast milk. In studies with beagle dogs, amounts of 3% of the administered dose have been found. Due to the risk of adverse reactions in children, it is recommended to discontinue breastfeeding or avoid administration of this medicine. CHILDREN Cetirizine can be used in children from 2 years of age, selecting the appropriate pharmaceutical form. Although its anticholinergic effects are not important, young children could be more susceptible to them, appearing a paradoxical reaction of excitation and tendency to convulsions. Safety and efficacy in children < 2 years have not been evaluated. RULES FOR CORRECT ADMINISTRATION - Tablets: take with a glass of liquid. The tablets can be split in half to obtain a 5 mg dose.DOSAGETablets:- Adults, oral: 10 mg/24 h.- Children and adolescents < 18 years, oral:* Adolescents > 12 years: 10 mg/24 h.* Children 6-12 years: 5 mg/12 h.* Children < 6 years: this medicinal product is not intended for these patients.- Elderly, oral: no dosage adjustment is required.DOSAGE IN LIVER FAILURENo dosage adjustment is required.DOSAGE IN RENAL FAILURE- Mild renal impairment (CLcr 50-79 ml/min): no dosage adjustment is required.- Moderate renal impairment (CLcr 30-49 ml/min): 5 mg/24 h.- Severe renal impairment (CLcr 10-30 ml/min): 5 mg every other day.- End-stage renal disease (CLcr < 10 ml/min): contraindicated. The dose should be individually adjusted in children with renal impairment based on age, weight and renal function. PRECAUTIONS - [RENAL INFECTION]. Adjust the dosage according to the degree of impairment. Not recommended in patients with severe renal impairment (CLcr less than 10 ml/minute) (see Contraindications). - [LIVER INFECTION]. Patients with chronic liver disease (hepatocellular, cholestatic and biliary cirrhosis) given 10 or 20 mg of cetirizine as a single dose had a 50% increase in half-life with a 40% decrease in clearance compared to healthy volunteers. Dose adjustment is only necessary in patients with impaired liver function if they have concomitant renal impairment. - [EPILEPSY]. Caution should be exercised in epileptic patients, as antihistamines have occasionally been associated with paradoxical hyperexcitability reactions, even at therapeutic doses, which may lower the seizure threshold.- Photosensitivity. Cetirizine may cause photosensitivity, so it is recommended not to sunbathe during treatment and to protect yourself with sunscreen. PRECAUTIONS RELATED TO EXCIPIENTS- This medicine contains lactose. Patients with hereditary [LACTOSE INTOLERANCE] or galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine. ADVERSE REACTIONS The side effects of cetirizine are usually mild and transient, and are more common during the first few days of treatment. Cetirizine produces less sedation than other H1 antihistamines, and its anticholinergic effects are practically non-existent, although their appearance cannot be ruled out. There is great interindividual variability with respect to the frequency and intensity of symptoms, affecting mainly young children and the elderly. The most common adverse reactions are:- Digestive. Cases of gastrointestinal discomfort such as [NAUSEA], [VOMITING], [CONSTIPATION], [DIARRHEA], [EPIGASTRIC PAIN], [ANOREXIA] or [DRY MOUTH] have been reported.- Neurological/psychological. Some cases of [DROWSY], [HEADACHE], [ASTHENIA], [DIZZINESS] and [EXCITABILITY] with [AGITATION] have been reported, mainly in children.- Allergic/dermatological. [HYPERSENSITIVITY REACTIONS] with [ANGIOEDEMA] may occur after systemic administration of antihistamines and occasionally [PHOTOSENSITIVITY REACTIONS] after intense exposure to sunlight, with [DERMATITIS], [PRURITUS], [EXANTHEMA] and [ERYTHEMA]. If these symptoms appear, it is recommended to split the dose. If they persist or worsen, it is recommended to discontinue treatment. OVERDOSE Symptoms: Cetirizine barely has any sedative or anticholinergic effects. In the event of an overdose, sedation is expected and sometimes, especially in children and the elderly, hyperexcitability. Treatment: Cetirizine is rapidly absorbed from the intestine, so in the event of an overdose, gastric lavage is ineffective unless it is performed within 30 minutes of ingestion. There is no known antidote. Symptomatic treatment will be followed.COMPOSITIONCETIRIZINE: 10 MILLIGRAMS - LACTOSE DIHYDROCHLORIDE (EXCIPIENT): 95.5 MILLIGRAMS - MONOHYDRATE