ACTION AND MECHANISM

[ANTI-ALLERGIC], [HISTAMINE H1 ANTAGONIST]. Loratadine is a piperidine derivative that potently, competitively, reversibly, and specifically blocks H1 receptors, reducing the systemic effects of histamine for a prolonged period. It causes vasoconstriction and decreased vascular permeability, reducing the redness and swelling associated with allergies. It partially alleviates symptoms associated with allergic reactions, such as eye redness and nasal congestion. It also produces a mild bronchodilator effect and reduces skin itching.

Loratadine barely crosses the blood-brain barrier, so it has virtually no significant sedative effects. It exhibits high selectivity for H1 receptors, lacking significant anticholinergic and antiserotonergic effects. Similarly, no cardiac effects have been observed in clinical trials.

SPECIAL WARNINGS

Due to the anti-allergic effects of this medication, it may produce false negatives in skin tests for hypersensitivity to antigenic extracts. It is recommended to discontinue administration of this medication at least 72 hours before the test.

PATIENT ADVICE

- It is recommended to administer this medication every day at the same time.

- The recommended dose should not be exceeded, as sedation may occur.

- It is advisable to avoid sun exposure during treatment.

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication. Cross-reactions with other antihistamines may occur, therefore the use of any H1 antihistamine is not recommended in patients who have experienced hypersensitivity to any compound in this group.

- [PORPHYRIA]. H1 antihistamines have been associated with the onset of porphyric attacks, so they are not considered safe in these patients.

ADVANCED AGE

No specific problems have been described that would require a dosage adjustment in elderly patients.

EFFECTS ON DRIVING

Although loratadine has not resulted in sedation in clinical trials, post-marketing use has shown the occurrence of cases of mild sedation, so it is recommended to avoid operating dangerous machinery, including automobiles, until there is reasonable certainty that the drug treatment does not adversely affect it.

PREGNANCY

Animal safety: Prolonged labor and reduced pup viability were observed at plasma levels (AUC) 10 times higher than those achieved with clinical doses in rats. However, no teratogenic effects were observed.

Safety in humans: A large amount of data shows that loratadine does not cause malformations or fetal toxicity. As a precautionary measure, its use is not recommended.

Effects on fertility: no specific studies have been conducted in humans.

PHARMACOKINETICS

- Absorption: Loratadine is well and rapidly absorbed orally, but undergoes extensive first-pass hepatic metabolism, resulting in the metabolite desloratadine. Following administration of 10 mg of loratadine, Cmax concentrations of 4.7 ng/ml (loratadine) and 4 ng/ml (desloratadine) are reached after 1–1.5 hours and 1.5–3.7 hours, respectively. Antihistamine effects appear after 1–3 hours, peak at 8–12 hours, and last up to 24 hours.

Effect of food : Taking loratadine with food increases the amount absorbed, but may delay absorption by up to one hour. However, this has no clinically significant effects.

- Distribution: Loratadine is highly bound to plasma proteins (97-99%), while desloratadine is moderately bound (73-77%). Loratadine is excreted in breast milk as desloratadine. It has great difficulty crossing the blood-brain barrier.

- Metabolism: Loratadine undergoes extensive hepatic metabolism, primarily via the CYP3A4 isoenzyme, and to a lesser extent CYP2D6, resulting in desloratadine, a carboxy-ethoxylated metabolite with potent antihistamine activity. This desloratadine is further metabolized into virtually inactive metabolites.

- Elimination: Loratadine is eliminated by hepatic metabolism and subsequent excretion in urine (40%) and feces (42%), primarily as conjugated metabolites. Less than 1% of the dose appears unchanged or as desloratadine. Elimination half-lives are 8–15 hours (loratadine) and 17–28 hours (desloratadine). Clearance appears to be dose-dependent, such that after administration of a 20 mg or 40 mg dose, values ​​of 202 and 142 ml/min/kg are obtained, respectively.

Pharmacokinetics in special situations:

- Elderly: In patients aged 66-78 years, Cmax and AUC values ​​are 50% higher than in younger patients.

- Renal insufficiency: In patients with severe renal insufficiency (CLcr less than 30 ml/minute) an increase in AUC and Cmax of 73% (loratadine) and 120% (desloratadine) has been observed, and accumulation of both substances may occur.

- Hepatic impairment: In patients with hepatic impairment, both Cmax and AUC are increased, potentially reaching up to twice the normal value. The elimination half-lives for loratadine and desloratadine were 24 hours and 37 hours, respectively, increasing with the degree of hepatic damage.

INDICATIONS

- Symptomatic treatment of allergic conditions such as [ALLERGIC RHINITIS] or [CHRONIC IDIOPATHIC URTICARIA].

INTERACTIONS

The use of loratadine with alcohol has not been shown to increase sedation. However, due to the risk of photosensitivity reactions from H1 antihistamine use, loratadine may potentiate the photosensitizing effects of other drugs. Interactions have been reported with:

- Enzyme inhibitors. Administration of loratadine with CYP3A4 inhibitors (erythromycin, ketoconazole) or CYP2D6 inhibitors (cimetidine) has resulted in plasma concentration increases of 40% (loratadine) and 46% (desloratadine) for erythromycin, 103% and 6% with cimetidine, and 307% and 73% with ketoconazole. However, no significant clinical alterations, including cardiotoxicity, have been observed.

LACTATION

Animal safety: no data available.

Safety in humans: loratadine is excreted in breast milk, so it is recommended to discontinue breastfeeding or avoid administering this medication.

CHILDREN

The safety and efficacy of loratadine in children under 2 years of age have not been evaluated, therefore its use is not recommended. In children over two years of age, loratadine has been used to treat allergic reactions, with a safety profile similar to that of adults. However, in theory, children may be more susceptible to adverse reactions, so extra caution is advised.

GUIDELINES FOR PROPER ADMINISTRATION

Administration with food: It is recommended to administer loratadine at approximately the same time each day and regardless of food.

Loratadine tablets should not be used in children under 2 years of age.

POSOLOGY

"COMPRESSED"

- Adults and adolescents > 6 years: 10 mg/24 hours.

- Children > 6 years (> 30 kg): 10 mg/24 hours.

- Children aged 2-12 years (< 30 kg): the 10 mg dose in tablet form is not recommended. Loratadine syrup is recommended.

- Children < 2 years: safety and efficacy have not been established in children under 2 years of age.

DOSAGE IN HEPATIC INSUFFICIENCY

The plasma half-lives of loratadine and its active metabolite increase with the degree of hepatic impairment. Use with caution in severe hepatic impairment.

DOSAGE IN RENAL INSUFFICIENCY

No dose adjustment is necessary.

PRECAUTIONS

- [RENAL IMPAIRMENT]. In patients with renal impairment, Cmax and AUC values ​​for loratadine and desloratadine are higher than in those with normal renal function. However, clearance and half-life levels are similar, so according to the manufacturer, dosage adjustment does not appear to be necessary. Nevertheless, close monitoring of these patients is advised, especially those with severe renal impairment (CLcr less than 30 ml/minute), as they may require lower doses.

- [HEPATIC IMPAIRMENT]. Loratadine is extensively metabolized in the liver. In cases of severe hepatic impairment, an increase in plasma concentration may occur, with the consequent risk of adverse effects. Dosage adjustment may be necessary in these patients depending on the degree of hepatic function (See Dosage).

- [EPILEPSY]. Caution should be exercised in epileptic patients, as antihistamines have occasionally been associated with paradoxical reactions of hyperexcitability, even at therapeutic doses, and could therefore lower the seizure threshold.

- Photosensitivity. Loratadine may cause photosensitivity, so it is recommended to avoid sun exposure during treatment and to protect yourself with sunscreen.

PRECAUTIONS RELATING TO EXCIPIENTS

This medicine contains lactose. Patients with hereditary lactose or galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

This medicine contains fructose. Patients with fructose intolerance should not take this medicine.

ADVERSE REACTIONS

The side effects of loratadine are usually mild and transient, and are typically dose-related. Non-sedating antihistamines generally produce the same side effects as sedating antihistamines, but much less frequently. In particular, sedation and anticholinergic effects are either nonexistent or very rare, provided that doses do not exceed the recommended amount.

The most frequent adverse reactions were headache, nervousness, and tiredness.

-Digestive disorders. Dry mouth is rare. Nausea, vomiting, constipation, diarrhea, or abdominal pain have also been reported.

- Liver disorders. Cases of [INCREASE TRANSAMINASES], [HEPATITIS] and [JAUNDICE] have been described.

- Cardiovascular disorders. Occasionally, tachycardia, palpitations, and other cardiac arrhythmias such as extrasystoles or heart block may occur. Hypotension or hypertension have also been reported.

- Neurological/psychological disorders. Headache (0.6%), mild drowsiness (1.2%), disorientation, ataxia, myasthenia, and vertigo are rare. Isolated cases of paradoxical excitability have been reported, especially in young children, with insomnia, nervousness, tremor, irritability, euphoria, delirium, palpitations, and even seizures.

- Genitourinary disorders. Cases of [DYSMENORRHEA] have been observed.

- Allergic/dermatological disorders. Hypersensitivity reactions may occur following systemic administration of antihistamines. Photosensitivity reactions may also occur following intense exposure to sunlight, with dermatitis, pruritus, rashes, and erythema.

- Eye disorders. Rarely, [GLAUCOMA] and [VISION DISORDERS] such as [BLURRED VISION] or [DIPLOPIA] may occur.

- Hematological disorders. Rarely, [HEMOLYTIC ANEMIA], [AGRANULOCYTOSIS], [LEUKOPENIA], [THROMBOCYTOPENIA] or [PANCYTOPENIA] may occur.

- Metabolic disorders: frequency unknown [INCREASED APPETITE], [WEIGHT GAIN].

- General disorders. [ASTHENIA] is common (1.2%). Some cases of [ALOPECIA] have been described.

OVERDOSE

Symptoms: There is limited data on loratadine poisoning. Sedation, tachycardia, and headache have been reported following administration of doses of 40–180 mg. However, in other studies, a single dose of 160 mg did not result in adverse effects. In children, overdose with the syrup at doses exceeding 10 mg of loratadine resulted in extrapyramidal symptoms and palpitations.

Treatment: There is no specific antidote. Treatment will consist of the usual measures aimed at promoting drug elimination. If less than three hours have passed since administration of the drug, vomiting may be induced with ipecac syrup, taking appropriate precautions to avoid aspiration of gastric contents, especially in children. Emesis should not be induced in unconscious or comatose patients. Gastric lavage with a 0.9% saline solution may also be used. In adults, tap water may be used, but as much as possible should be removed before the next instillation. Administration of activated charcoal and saline laxatives, which rapidly dilute the intestinal contents, may also be helpful.

Symptomatic and supportive treatment is recommended.

Loratadine is not removed by hemodialysis, and it is unknown whether it is removed by peritoneal dialysis.