Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Alliance Pharmaceuticals Limited, Avonbridge House, Chippenham, Wiltshire, SN15 2BB, United Kingdom
Atarax is contra-indicated in the following:
Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Hydroxyzine has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been cases of QT interval prolongation and torsade de pointes in patients taking hydroxyzine. Most of these patients had other risk factors, electrolyte abnormalities and concomitant treatment that may have been contributory (see section 4.8).
Hydroxyzine should be used at the lowest effective dose and for the shortest possible duration.
Treatment with hydroxyzine should be stopped if signs or symptoms occur that may be associated with cardiac arrhythmia, and the patients should seek immediate medical attention.
Patients should be advised to promptly report any cardiac symptoms.
Due to its sedative properties, use of hydroxyzine should be avoided in severe liver disease due to an increased risk of coma, and in patients with hepatic failure due to possibility of hepatic encephalopathy.
Hydroxyzine elimination is impaired in patients with hepatic dysfunction secondary to primary biliary cirrhosis. Dosage should be modified for patients with hepatic impairment (see Section 4.2 ‘Posology and Method of Administration’).
Atarax should be used with caution in patients with impaired renal function (see Section 4.2 ‘Posology and Method of Administration’). It is uncertain whether the drug may accumulate or have other adverse effects in such patients. Atarax is completely metabolised and one of the metabolites is the active metabolite cetirizine. Cetirizine is renally excreted and clearance is reduced in patients with moderate renal impairment and on dialysis compared to normal volunteers.
Hydroxyzine is not recommended in elderly patients because of a decrease of hydroxyzine elimination in this population as compared to adults and the greater risk of adverse reactions (e.g. anticholinergic effects) (see sections 4.2 and 4.8). In elderly patients, it is recommended to reduce the dose of hydroxyzine due to a possible increase in the volume of distribution, prolonged action, and the possible effect of age-related changes on pharmacologic functions, including hepatic metabolism and renal excretion (see Section 4.2 ‘Posology and Method of Administration’ and Section 5.2 ‘Pharmacokinetic properties’)
Because of its potential antimuscarinic actions, Atarax should be used with caution in patients suffering from angle-closure glaucoma, urinary retention, prostatic hyperplasia, or pyroduodenal obstruction.
Caution is required in patients suffering the following conditions:
Dosage adjustments may be required if Atarax is used simultaneously with other CNS depressants or with drugs having antimuscarinic properties (see section 4.5 ‘Interaction with other medicinal products and other forms of interaction’).
The concomitant use of alcohol and hydroxyzine should be avoided (see section 4.5 ‘Interaction with other medicinal products and other forms of interaction’).
Treatment should be stopped for one week before skin testing for allergy is undertaken, and for 96 hours prior to a methocholine test.
Children and the elderly are more susceptible to side-effects.
Patients should be warned of impaired judgement and dexterity.
Atarax 10mg Film-coated tablets contain Sunset Yellow (E110) which may cause allergic reactions.
Co-administration of hydroxyzine with drugs known to prolong the QT interval and/or induce Torsade de Pointes e.g. class IA (e.g. quinidine, disopyramide) and III antiarrhythmics (e.g. amiodarone, sotalol), some antihistamines, some antipsychotics (e.g. haloperidol), some antidepressants (e.g. citalopram, escitalopram), some antimalarial drugs (e.g. mefloquine), some antibiotics (e.g. erythromycin, levofloxacin, moxifloxacin), some antifungal agents (e.g. pentamidine), some gastro-intestinal medicines (e.g. prucalopride), some medicines used in cancer (e.g., toremifene, vandetanib), methadone, increase the risk of cardiac arrhythmia. Therefore, the combination is contra-indicated (see section 4.3).
Caution with bradycardia and hypokalaemia-inducing drugs.
Hydroxyzine is metabolized by alcohol dehydrogenase and CYP3A4/5 and an increase in hydroxyzine blood concentrations may be expected when hydroxyzine is co-administered with drugs known to be potent inhibitors of these enzymes.
Atarax may also have the following interactions:
Methocholine test: Treatment should be stopped for 96 hours prior to a methocholine test, to avoid effects on the test results (see section 4.4 ‘Special warnings and precautions for use’).
Skin testing for allergy: Treatment should be stopped at least one week before skin testing for allergy to avoid effects on the test results (see section 4.4 ‘Special warnings and precautions for use’).
CNS depressants: Patients should be warned that Atarax may enhance their response to alcohol, barbiturates, benzodiazepines, hypnotics, opioids, anxiolytics, antipsychotics, antidepressents, antiemetics, antiepileptics, other antihistamines, skeletal muscle relaxants, sedatives, anaesthetics and other CNS depressants (see section 4.4 ‘Special warnings and precautions for use’).
Antimuscarinics: Antimuscarinic side effects (both peripheral and central) may be increased if Atarax is given with antimuscarinics such as atropine and some antidepressants (both tricyclics and MAOIs) (see section 4.4 ‘Special warnings and precautions for use’).
Adrenaline: Hydroxyzine has been shown to inhibit and reverse the vasopressor effect of adrenaline (see Section 4.9 ‘Overdose’).
Anticholinergic agents: Additive anticholinergic effects may occur if hydroxyzine is administered concomitantly with other anticholinergic agents.
Anticholinesterase drugs: Hydroxyzine may antagonise the effects of anticholinesterase drugs.
Betahistine: Hydroxyzine may antagonise the effects of betahistine.
Cimetidine: Cimetidine, 600mg twice a day, has been shown to increase the serum concentrations of hydroxyzine and to decrease peak concentrations of the metabolite cetirizine.
CYP2D6 & cytochrome P450: Hydroxyzine is an inhibitor of CYP2D6 and may cause drug-drug interactions with CYP2D6 substrates. Cetirizine does not interact with other drug substances via cytochrome P450.
Drugs which have effects on the brain: Drugs which have effects on the brain will interact with antihistamines.
Drugs that affect the hepatic microsomal enzyme system: Metabolism may be reduced in patients concomitantly receiving drugs that affect the hepatic microsomal enzyme system. Decreased metabolism may result in accumulation of potentially toxic concentrations of unchanged antihistamine.
Ototoxic drugs: It has been suggested that some sedating antihistamines could mask the warning signs of damage caused by ototoxic drugs such as aminoglycoside antibiotics.
Porter-Silber reaction or the Glenn-Nelson method: Hydroxyzine has been reported to cause falsely elevated urinary concentrations of 17-hydroxycorticosteroids when the Porter-Silber reaction or the Glenn-Nelson method is used.
Atarax should not be used during pregnancy (see section 4.3 ‘Contraindications’).
Clinical data in humans are inadequate to establish safety in early pregnancy.
The use of sedating antihistamines in the latter part of the third trimester may cause adverse effects in neonates such as irritability, paradoxical excitability, and tremor.
Animal studies have shown reproductive toxicity. Foetal abnormalities have been reported when hydroxyzine was administered, at doses substantially above the human therapeutic dose, to the pregnant mouse, rat and rabbit.
Hydroxyzine crosses the placental barrier which may lead to higher foetal than maternal concentrations.
The following events were observed in a neonate whose mother received high dose (600mg per day) hydroxyzine during pregnancy; hypotonia, movement disorders including extrapyramidal disorders, clonic movements, tachypnea and poor feeding.
It is expected that Atarax may be excreted into breast milk. The effects on the nursing infant are unknown. Atarax should not be given to nursing mothers (see section 4.3 'Contraindications).
Patients should be warned that Atarax may impair their ability to perform activities requiring mental alertness or physical co-ordination such as operating machinery or driving a vehicle. Concomitant use of hydroxyzine with alcohol or other CNS depressants should be avoided as this may aggravate these effects (see section 4.5 'Interaction with other medicinal products and other forms of interaction).
The most common adverse effect of the sedating antihistamines is CNS depression. Effects vary from slight drowsiness to deep sleep, and include lassitude, dizziness, and incoordination. Paradoxical stimulation may occasionally occur, especially at high doses and in children and the elderly. If sedative effects occur, they may diminish after a few days of treatment. Other common adverse effects include headache, psychomotor impairment and antimuscarinic effects.
Undesirable effects are listed by MedDRA System Organ Classes.
Assessment of undesirable effects is based on the following frequency groupings: Very common: ≥1/10, Common: ≥1/100 to <1/10, Uncommon: ≥1/1,000 to <1/100, Rare: ≥1/10,000 to <1/1,000, Very rare: <1/10,000, Not known: cannot be estimated from the available data.
Not known: blood disorders, including agranulocytosis, leucopenia, haemolytic anaemia, and thrombocytopenia
Not known: hypersensitivity reactions, anaphylaxis, angioedema
Not known: porphyria, anorexia
Not known: agitation, confusion, disorientation, hallucinations, sleep disturbances, depression, increased anxiety, nightmares
Not known: dyskinesia4, insomnia, sedation, drowsiness, dizziness, weakness, headache, tremor1 convulsions2, psychomotor impairment, paraesthesias, extrapyramidal effects, seizure, coma, somnolence, disturbance in attention, involuntary motor activity3, ataxia, slurred speech, bitter taste in mouth, faintness
Not known: accommodation disorder, blurred vision
Not known: tinnitus, labrynthitis, vertigo
Not known: ventricular arrhythmias (e.g. Torsade de Pointes), QT interval prolongation (see section 4.4), tachycardia, palpitation
Not known: hypotension, flushing
Not known: bronchospasm, thickened respiratory tract secretions, wheezing, nasal stuffiness, dryness of throat
Not known: constipation, dryness of the mouth, nausea, vomiting, increased gastric reflux, diarrhoea, epigastric pain, increased GI peristalsis
Not known: liver dysfunction
Very rare: Stevens-Johnson syndrome, erythema multiforme
Not known: dermatitis, fixed drug eruption, pruritis, erythema, papular rash, sweating increased, urticaria, hair loss, eczema, acute generalised exanthematous pustulosis (AGEP), toxic epidermal necrolysis
Not known: myalgia
Not known: urinary retention, dysuria
Not known: priapism, impotence, early menses
Not known: fatigue, malaise, lassitude, pyrexia, dryness of respiratory mucosae, asthenia, tightness of chest, irritability, chills
Not known: liver function tests abnormal
Footnotes:
1,2,3 reported usually with doses considerably higher than those recommended. Continuous therapy with over 1g/day has been employed in some patients without these effects having been encountered
4 dyskinesia may follow termination of prolonged antihistamine therapy.
Children and the elderly are more susceptible to side-effects.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.
Hydroxyzine hydrochloride has been reported to be incompatible with aminophylline, benzylpenicillin salts, chloramphenicol sodium succinate, dimenhydrinate, doxorubicin hydrochloride (in a liposomal formulation), thioridazine, and some soluble barbiturates.
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