Atarax®: composition and pharmaceutical form
Atarax® comes as film-coated tablets containing 10 mg or 25 mg of hydroxyzine hydrochloride, and as a syrup in which 1 ml contains 2 mg of the same substance.
The syrup is convenient for children and for adjusting the dose precisely to body weight, but it has its own compositional features: it contains sucrose and a small amount of ethanol. The tablets contain lactose. These details are not a formality — they determine which form suits whom.
How Atarax® works
Hydroxyzine hydrochloride does not suppress the activity of the cerebral cortex; its action is probably linked to inhibition of the activity of certain subcortical areas of the central nervous system. The antihistamine and bronchodilator effects are confirmed both experimentally and clinically, and the antiemetic action has been shown in the apomorphine and veratrine tests.
At therapeutic doses hydroxyzine does not increase gastric secretion or its acidity and in most cases produces a moderate antisecretory effect. In healthy adults and in children it reduced the wheal-and-flare reaction after intradermal administration of histamine or antigens and proved able to reduce itching in various forms of urticaria, eczema and dermatitis. In hepatic impairment the antihistamine action of a single dose may stretch to 96 hours.
Indications
Atarax® is used for the symptomatic treatment of anxiety in adults, the symptomatic treatment of itching and premedication before surgical procedures.
Note the word "symptomatic": the medicine relieves the manifestations rather than removing their cause. Hence the requirement to use the lowest effective dose for the shortest possible course.
Method of use and dosage
The dose is chosen individually within the recommended range, guided by the patient's response. For adults and children over 40 kg the maximum daily dose is 100 mg.
| Indication or group | Dose |
|---|---|
| Anxiety | 50 mg a day in 2–3 intakes; in severe cases up to 100 mg a day |
| Itching | start with 25 mg before sleep and, if needed, continue with 25 mg 3–4 times a day |
| Premedication before an operation | 50 mg in two intakes or 100 mg as a single oral dose |
| Children from 12 months with itching | 1–2 mg per kg of body weight a day in several intakes |
| Children from 12 months, premedication | 0.6 mg per kg as a single oral dose; no more than 2 mg per kg a day in total |
| Elderly patients | the medicine is not recommended; if prescribed, half the usual dose, a maximum of 50 mg a day |
In hepatic impairment the daily dose is reduced by a third. In moderate and severe renal impairment the dose is also lowered: the elimination of cetirizine, a metabolite of hydroxyzine, slows down. For children and adolescents under 40 kg the limit is 2 mg per kg a day and, above 40 kg, 100 mg a day.
Contraindications
Most of the restrictions relate to the medicine's influence on heart rhythm.
- hypersensitivity to hydroxyzine, cetirizine, other piperazine derivatives, aminophylline, ethylenediamine or any excipient;
- porphyria;
- congenital or acquired prolongation of the QT interval;
- risk factors for QT prolongation: cardiovascular disease, significant electrolyte disturbances — hypokalaemia, hypomagnesaemia;
- sudden cardiac death in the family;
- marked bradycardia;
- concomitant use of medicines that prolong the QT interval or cause torsade de pointes arrhythmia;
- pregnancy and the breastfeeding period.
Special warnings and precautions
The use of hydroxyzine has been linked to prolongation of the QT interval on the electrocardiogram and, after the medicine reached the market, reports were received of QT prolongation and of torsade de pointes ventricular tachycardia. Most of those patients also had other risk factors — electrolyte disturbances and concomitant use of other medicines. Hence the rule: the lowest effective dose, the shortest possible course and, if symptoms appear that may relate to a rhythm disturbance, treatment is stopped and a doctor contacted immediately. The patient should be told plainly to report any cardiac symptoms straight away.
Who needs particular caution
- patients prone to seizures; in children seizures were seen more often than in adults;
- small children — they are more vulnerable to undesirable effects on the nervous system;
- in glaucoma, difficulty emptying the bladder, weakened intestinal peristalsis, myasthenia and dementia — because of the medicine's anticholinergic action;
- with concomitant use of agents that depress the nervous system, or of anticholinergics, a dose adjustment may be needed;
- alcohol should be avoided during treatment;
- in elderly people the medicine is not recommended: elimination is slower and the risk of adverse reactions higher;
- the syrup contains 0.75 g of sucrose per 1 ml and is unsuitable in hereditary fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency, and in diabetes the sucrose is taken into account at doses above 6.5 ml;
- the syrup contains 0.1% ethanol, which matters in alcoholic disease, in children and in patients with liver disease or epilepsy; the tablets contain lactose and are unsuitable in case of intolerance to it.
Drug interactions
Categorically incompatible with hydroxyzine are medicines that prolong the QT interval or cause torsade de pointes arrhythmia: class IA antiarrhythmics — quinidine, disopyramide — and class III — amiodarone, sotalol, some antihistamines and antipsychotics including haloperidol, certain antidepressants, in particular citalopram and escitalopram, the antimalarials mefloquine and hydroxychloroquine, some antibiotics — erythromycin, levofloxacin, moxifloxacin — and also pentamidine, prucalopride, toremifene, vandetanib and methadone. Agents that cause bradycardia and hypokalaemia call for caution.
Agents that depress the central nervous system and anticholinergics enhance the action of hydroxyzine, as does alcohol. Hydroxyzine itself acts in the opposite direction to betahistine and cholinesterase inhibitors, weakens the pressor effect of adrenaline and, in experiments in rats, reduced the anticonvulsant action of phenytoin. Cimetidine at 600 mg twice a day raised the serum concentration of hydroxyzine by 36% and lowered the cetirizine level by 20%. Hydroxyzine inhibits CYP2D6 and at high doses may interact with substrates of that enzyme; it is itself metabolised by alcohol dehydrogenase and CYP3A4/5, so strong inhibitors of those pathways raise its concentration. Before skin allergy tests or a bronchial provocation test with methacholine, treatment is interrupted at least 5 days beforehand, otherwise the results will be distorted. Concomitant use with MAO inhibitors is avoided.
Pregnancy and breastfeeding
Hydroxyzine is contraindicated in pregnancy. Women of childbearing age must use reliable contraception for the duration of treatment. Animal studies showed reproductive toxicity, and hydroxyzine itself crosses the placental barrier and reaches a higher concentration in the foetus than in the mother. There are at present no significant epidemiological data on use in pregnancy.
In newborns whose mothers received hydroxyzine late in pregnancy or during labour, reduced muscle tone, movement disorders including extrapyramidal ones, clonic movements, depression of the central nervous system, hypoxia and urinary retention were seen immediately or a few hours after birth. During breastfeeding the medicine is likewise contraindicated: cetirizine, the main metabolite, passes into breast milk, and severe adverse reactions have been described in breastfed children. If treatment is necessary, breastfeeding is stopped.
Adverse effects
Adverse reactions relate above all to the depressant or, conversely, paradoxically stimulating action on the nervous system, to the anticholinergic effect and to hypersensitivity reactions. In clinical trials, drowsiness, headache, dry mouth and fatigue occurred in no fewer than 1% of patients.
- common: sedation, fatigue;
- uncommon: dizziness, insomnia, tremor, agitation, confusion, nausea, malaise, fever;
- rare: disorientation, hallucinations, seizures, dyskinesia, disturbances of accommodation, blurred vision, tachycardia, a fall in blood pressure, constipation, vomiting;
- rare in the skin and liver: itching, erythematous and maculopapular rash, urticaria, dermatitis, abnormalities in liver tests;
- rare: urinary retention, hypersensitivity reactions;
- very rare: anaphylactic shock, bronchospasm, angioedema, increased sweating, fixed drug eruption, acute generalised exanthematous pustulosis, erythema multiforme, Stevens-Johnson syndrome;
- frequency not known: fainting, ventricular rhythm disturbances including torsade de pointes, QT interval prolongation, hepatitis, bullous skin lesions;
- through the metabolite cetirizine, thrombocytopenia, aggression, depression, tics, dystonia, paraesthesia, oculogyric crises, diarrhoea, urinary disorders, asthenia, oedema and weight gain are also possible.
Any cardiac symptom — palpitations, fainting, irregular beats — is a reason to stop the medicine at once and see a doctor without waiting for the scheduled visit.
Overdose
The symptoms of a significant overdose relate mainly to excessive anticholinergic action and to depression or paradoxical excitation of the nervous system: nausea, vomiting, tachycardia, fever, drowsiness, disturbed pupillary reflex, tremor, confusion or hallucinations. Then a fall in the level of consciousness, respiratory depression, seizures, a drop in blood pressure, rhythm disturbances including bradycardia, deepening coma and cardiovascular collapse are possible.
Control of the airway, breathing and circulation is required, with continuous ECG recording and oxygen; monitoring of cardiac activity and blood pressure continues for 24 hours until the symptoms disappear. Where consciousness is disturbed, it is established whether the patient took other medicines or alcohol and, if necessary, oxygen, naloxone, glucose and thiamine are given. If a vasoconstrictor is needed, noradrenaline or metaraminol is used, but not adrenaline. Emetics are contraindicated where there is a risk of disturbed consciousness, coma or seizures because of the threat of aspiration pneumonia; with a clinically significant intake, gastric lavage after tracheal intubation is possible. Data on the efficacy of activated charcoal are scarce, and the benefit of haemodialysis and haemoperfusion is doubtful. There is no specific antidote; the literature describes the use of physostigmine in severe, life-threatening anticholinergic syndrome, though it is not used merely to keep the patient awake and is avoided with concomitant tricyclic antidepressants and in disorders of cardiac conduction.
How to get a prescription for Atarax® online
Atarax® is a prescription-only medicine, and the main reason is its influence on heart rhythm: before prescribing, the doctor assesses the cardiovascular history, electrolyte disturbances and the whole list of medicines being taken. During the online consultation the doctor will go through your situation and decide whether the medicine is suitable and in which form.
If there are no contraindications, the doctor will issue an electronic prescription, choose the dose and the length of the course and explain at which symptoms the medicine must be stopped immediately.
