ACTION AND MECHANISM

[ANTI-ALLERGIC], [HISTAMINE H1 ANTAGONIST]. Ebastine is a piperidine derivative that potently, competitively, reversibly, and specifically blocks H1 receptors, reducing the systemic effects of histamine in a prolonged manner. It causes vasoconstriction and decreased vascular permeability, reducing the redness and edema associated with allergies. It partially alleviates symptoms associated with allergic processes, such as eye redness and nasal congestion. It also produces a mild bronchodilator effect and reduces skin itching. Clinical experience also suggests that ebastine can inhibit the release of histamine from mast cells.

Ebastine barely crosses the blood-brain barrier, and therefore has virtually no significant sedative effects. It exhibits high selectivity for H1 receptors and lacks significant anticholinergic and antiserotonergic effects. Similarly, no cardiac effects have been observed in clinical trials using doses up to 100 mg.

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.

- Monitoring of cardiac function and electrocardiogram is recommended in patients with heart disease or in those receiving ebastine along with erythromycin, ketoconazole or antiarrhythmic drugs, due to the risk of QTc interval prolongation.

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 in elderly patients that would require a dosage adjustment. The pharmacokinetic profile of elderly and younger individuals is very similar.

EFFECTS ON DRIVING

Although in clinical trials ebastine has not resulted in sedation at a dose of 30 mg/24 hours, 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: no direct or indirect harmful effects on reproduction in animals were observed.

Safety in pregnant women: Adequate and well-controlled studies in humans have not been conducted. Use of this drug is only acceptable when safer therapeutic alternatives are unavailable.

Effects on fertility: No specific studies have been conducted in humans. Animal studies have not shown fetotoxic or teratogenic effects of ebastine.

PHARMACOKINETICS

- Absorption: Ebastine is rapidly absorbed from the intestine after oral administration, undergoing extensive first-pass hepatic metabolism that generates an active metabolite, carebastine. The Cmax of ebastine obtained after a 20 mg dose is 2.8 ng/ml, while after a 10 mg dose, a Cmax of carebastine of 80-100 ng/ml is reached at 2.6-4 hours. Antihistamine activity begins within 1-3 hours, is maximal at 8-12 hours, and can last for up to 48 hours. After discontinuation of a 5-day treatment, antihistamine effects were observed for 72 hours, primarily due to ebastine metabolites, especially carebastine.

Effect of food : Food increases the AUC of carebastine by 1.5-2 times, although this increase does not modify Tmax. Administration of ebastine with food does not significantly alter its clinical effect.

- Distribution: Ebastine and carebastine are strongly bound to plasma proteins (95%).

- Metabolism: Ebastine is extensively metabolized by the CYP3A4 isoenzyme, resulting in the active metabolite carebastine.

- Elimination: Ebastine is primarily eliminated by hepatic metabolism. 66% of the dose appears in the urine, mainly as conjugated metabolites. Small amounts may also appear in the feces (6%). The elimination half-life of ebastine is 15-19 hours.

Pharmacokinetics in special situations : no significant pharmacokinetic differences have been observed between patients over 65 years of age and younger patients, nor between individuals with different degrees of renal or hepatic impairment compared to healthy patients.

INDICATIONS

- [SEASONAL ALLERGIC RHINITIS] or [PERENNIAL ALLERGIC RHINITIS], associated or not with [ALLERGIC CONJUNCTIVITIS].

INTERACTIONS

No drug interactions have been observed with ebastine. The use of ebastine with alcohol has not been shown to increase sedation. However, due to the risk of photosensitivity reactions associated with H1 antihistamines, ebastine may potentiate the photosensitizing effects of other drugs.

- Erythromycin, ketoconazole. There have been some cases of slight QTc interval prolongation, of approximately 10 ms. It is unknown whether this effect is due to enzyme inhibition of CYP3A4 by macrolides or azole antifungals, or to the cardiac effects of these drugs themselves. Extreme caution is advised in patients receiving ebastine concurrently with either of these drugs.

LACTATION

Animal safety: no data available.

Safety in humans: It is unknown whether ebastine is excreted in breast milk, but other antihistamines are. Both ebastine and its metabolite, carebastine, are highly protein bound (>97%), suggesting that excretion in breast milk does not occur. However, it is recommended to discontinue breastfeeding or avoid administering this medication.

CHILDREN

Safety and efficacy have not been evaluated in children under 2 years of age, therefore its use is not recommended.

The 10 mg and 20 mg doses are not indicated for children between 2-12 years old, so in these cases it is recommended to use the oral solution, adjusting the dose according to age.

GUIDELINES FOR PROPER ADMINISTRATION

- Tablets: swallow whole, with the help of a glass of liquid, preferably water.

POSOLOGY

"DOSAGE FOR TABLETS"

- Adults: 10-20 mg/24 h.

- Children and adolescents < 18 years:

* Adolescents aged 12 years and over: no dosage adjustment required.

DOSAGE IN HEPATIC INSUFFICIENCY

- Mild to moderate hepatic impairment (Child-Pugh class A): no dosage adjustment required.

- Severe hepatic impairment (Child-Pugh class C): maximum dose 10 mg/24 h.

DOSAGE IN RENAL INSUFFICIENCY

No dosage adjustment is required.

PRECAUTIONS

[HEPATIC IMPAIRMENT]. Ebastine is extensively metabolized in the liver. In cases of hepatic impairment, an increase in plasma concentration may occur. It is recommended not to exceed a dose of 10 mg/24 hours in patients with severe hepatic impairment, while in those with mild or moderate impairment, no precautions are necessary, although monitoring of these patients is advisable (See Dosage and Administration).

- [CARDIAC ARRHYTHMIA]. Patients with cardiac risk factors, such as those with [BRADYCARDIA], [QT INTERVAL PROLONGATION], [HYPOKALEMIA], or those receiving treatment with drugs that affect the QT interval or inhibit the metabolism of ebastine (See Interactions). Clinical trials have shown that ebastine does not have significant effects on the heart at doses up to 100 mg/24 hours, but this cannot be ruled out; therefore, monitoring of cardiac function is recommended in these patients.

- [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. Ebastine may cause photosensitivity, so it is recommended to avoid sun exposure during treatment and to protect yourself with sunscreens.

- Acute allergic processes. Because ebastine can take around three hours to produce pharmacological effects, its use is not recommended in severe acute allergic processes.

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 ebastine 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 absent or very rare, provided doses are not exceeded. In clinical trials with 2,100 patients, ebastine caused adverse reactions in only 3.7% more patients than placebo. The most common adverse reactions are:

- Immune system disorders: [HYPERSENSITIVITY REACTIONS] may occur following systemic administration of antihistamines.

- Metabolism and nutrition disorders: frequency poorly known [INCREASED APPETITE], [WEIGHT GAIN]

- Nervous system disorders: mild headache or drowsiness is common. Some cases of dizziness, disorientation, ataxia, myasthenia, vertigo, hypoesthesia, dysgeusia, and asthenia have also been reported. As with other antihistamines, isolated cases of paradoxical excitability may occur, especially in young children, with insomnia and nervousness, tremor, irritability, euphoria, delirium, palpitations, and even seizures.

- Psychiatric disorders: [INSOMNIA], [NERVOUSNESS].

- Cardiovascular disorders. Occasionally, tachycardia, palpitations, and other cardiac arrhythmias such as extrasystoles or heart block may occur. Hypotension or hypertension have also been reported. Mild QT interval prolongation has been described in certain patients, such as those treated with high doses of erythromycin or ketoconazole.

- Respiratory, thoracic and mediastinal disorders Some cases of [EPISTAXIS] and [SINUSITIS] have been described.

- Gastrointestinal disorders: dry mouth is rare. Cases of nausea, vomiting, constipation, diarrhea, or epigastric pain have also been reported.

- Hepatobiliary disorders: some cases of [HEPATITIS], [CHOLESTASIS], [INCREASE TRANSAMINASES], [INCREASE ALKALINE PHOSPHATASE] and [HYPERBILIRUBINEMIA] have been reported

- Skin and subcutaneous tissue disorders: [PHOTOSENSITIVITY REACTIONS] may occur after intense exposure to sunlight, [DERMATITIS], [URTICARIA], [PRURITUS], [SKIN ERUPTIONS] and [ERYTHEMA].

- Reproductive system and breast disorders: cases of [DYSMENORRHEA] have been observed.

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

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

- General disorders and administration site conditions: some cases of [EDEMA] and [ASTHENIA] have been reported

OVERDOSE

Symptoms: There is limited data on ebastine poisoning. In a clinical trial administering doses of up to 100 mg of ebastine, no adverse reactions were observed.

Treatment: There is no specific antidote. Treatment will consist of standard measures to promote drug elimination. Symptomatic and supportive treatment is recommended, with monitoring of vital signs and ECG.