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l SIDE-EFFECTS Aggression . agranulocytosis . anxiety . appetite abnormal . arrhythmias . bronchial secretion

viscosity increased . chest tightness . chills . confusion . constipation . coordination abnormal . diarrhoea . dizziness . drowsiness . dry mouth . dry throat. epigastric

distress . epistaxis .fatigue . haemolytic anaemia . hallucination . headache . hepatic disorders . hyperhidrosis . hypotension . insomnia . labyrinthitis . leucopenia . menstruation irregular. mood altered . nasal complaints . nausea . neuritis . oedema . palpitations . paraesthesia . photosensitivity reaction . seizure . skin reactions . thrombocytopenia .tinnitus .tremor. urinary disorders . vertigo . vision disorders . vomiting . weight increased . wheezing

l PREGNANCY Most manufacturers of antihistamines advise

avoiding their use during pregnancy; however, there is no

evidence of teratogenicity. Use in the latter part of the

third trimester may cause adverse effects in neonates such

as irritability, paradoxical excitability, and tremor.

l BREAST FEEDING Most antihistamines are present in

breast milk in varying amounts; although not known to be

harmful, most manufacturers advise avoiding their use in

mothers who are breast-feeding.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Drowsiness may affect

performance of skilled tasks (e.g. driving); sedating effects

enhanced by alcohol.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: oral suspension, oral

solution

Tablet

CAUTIONARY AND ADVISORY LABELS 2

▶ Periactin (Teva UK Ltd)

Cyproheptadine hydrochloride 4 mg Periactin 4mg tablets | 30 tablet p £5.99 DT = £5.99

Hydroxyzine hydrochloride 30-Mar-2017

l DRUG ACTION Hydroxyzine is a sedating antihistamine

which exerts its actions by antagonising the effects of

histamine.

l INDICATIONS AND DOSE

Pruritus

▶ BY MOUTH

▶ Child 6 months–5 years: 5–15 mg daily in divided doses,

dose adjusted according to weight; maximum 2 mg/kg

per day

▶ Child 6–17 years (body-weight up to 40 kg): Initially

15–25 mg daily in divided doses, dose increased as

necessary, adjusted according to weight; maximum

2 mg/kg per day

▶ Child 6–17 years (body-weight 40 kg and above): Initially

15–25 mg daily in divided doses, increased if necessary

to 50–100 mg daily in divided doses, dose adjusted

according to weight

▶ Adult: Initially 25 mg daily, dose to be taken at night;

increased if necessary to 25 mg 3–4 times a day

▶ Elderly: Initially 25 mg daily, dose to be taken at night;

increased if necessary to 25 mg twice daily

IMPORTANT SAFETY INFORMATION

MHRA/CHM ADVICE: RISK OF QT-INTERVAL PROLONGATION AND

TORSADE DE POINTES (APRIL 2015)

Following concerns of heart rhythm abnormalities, the

safety and efficacy of hydroxyzine has been reviewed by

the European Medicines Agency. The review concludes

that hydroxyzine is associated with a small risk of QTinterval prolongation and torsade de pointes; these

events are most likely to occur in patients who have risk

factors for QT prolongation, e.g. concomitant use of

drugs that prolong the QT-interval, cardiovascular

disease, family history of sudden cardiac death,

significant electrolyte imbalance (low plasma-potassium

or plasma-magnesium concentrations), or significant

bradycardia. To minimise the risk of such adverse effects,

the following dose restrictions have been made and new

cautions and contra-indications added:

. Hydroxyzine is contra-indicated in patients with

prolonged QT-interval or who have risk factors for QTinterval prolongation;

. Avoid use in the elderly due to increased susceptibility

to the side-effects of hydroxyzine;

. Consider the risks of QT-interval prolongation and

torsade de pointes before prescribing to patients

taking drugs that lower heart rate or plasmapotassium concentration;

. In children with body-weight up to 40 kg, the

maximum daily dose is 2 mg/kg;

. In adults, the maximum daily dose is 100 mg;

. In the elderly, the maximum daily dose is 50 mg (if use

of hydroxyzine cannot be avoided);

. The lowest effective dose for the shortest period of

time should be prescribed.

l CONTRA-INDICATIONS Acquired or congenital QT interval

prolongation . predisposition to QT interval prolongation

CONTRA-INDICATIONS, FURTHER INFORMATION

▶ QT interval prolongation Risk factors for QT interval

prolongation include significant electrolyte imbalance,

bradycardia, cardiovascular disease, and family history of

sudden cardiac death.

l CAUTIONS Bladder outflow obstruction . breathing

problems . cardiovascular disease . children . decreased

gastrointestinal motility . dementia . elderly . epilepsy . hypertension . hyperthyroidism . myasthenia gravis . prostatic hypertrophy (in adults). pyloroduodenal

obstruction . stenosing peptic ulcer. susceptibility to

angle-closure glaucoma . urinary retention

CAUTIONS, FURTHER INFORMATION

▶ Elderly Elderly patients are particularly susceptible to sideeffects; manufacturers advise avoid or reduce dose.

▶ Children Children have an increased susceptibility to sideeffects, particularly CNS effects.

l INTERACTIONS → Appendix 1: antihistamines, sedating

l SIDE-EFFECTS

▶ Rare or very rare Severe cutaneous adverse reactions

(SCARs). skin reactions

▶ Frequency not known Agranulocytosis . alopecia . anticholinergic syndrome . anxiety . appetite decreased . arrhythmias . asthenia . blood disorder. bronchial

secretion viscosity increased . chest tightness . chills . coma . concentration impaired . confusion . constipation . depression . diarrhoea . dizziness . drowsiness . dry mouth . dry throat. dyskinesia (on discontinuation). epigastric

pain . fever. flushing . gastrointestinal disorders . haemolytic anaemia . hallucination . headache . hepatic

function abnormal . hyperhidrosis . hypotension . irritability . labyrinthitis . leucopenia . malaise . menstruation irregular. movement disorders . myalgia . nasal congestion . nausea . palpitations . paraesthesia . QT

interval prolongation .respiratory disorders .respiratory

tract dryness . seizure (with high doses). sexual

dysfunction . sleep disorders . speech slurred .taste bitter. thrombocytopenia .tinnitus .tremor (with high doses). urinary disorders . vertigo . vision disorders . vomiting

SIDE-EFFECTS, FURTHER INFORMATION Paradoxical

stimulation may occur rarely, especially with high doses or

in the elderly. Drowsiness may diminish after a few days of

treatment.

BNF 78 Allergic conditions 285

Respiratory system

3

l ALLERGY AND CROSS-SENSITIVITY Manufacturer advises

hydroxyzine should be avoided in patients with previous

hypersensitivity to cetirizine or other piperazine

derivatives, and aminophylline.

l PREGNANCY Manufacturers advise avoid—toxicity in

animal studies with higher doses. Use in the latter part of

the third trimester may cause irritability, paradoxical

excitability, and tremor in the neonate.

l BREAST FEEDING Manufacturer advises avoid—expected

to be present in milk but effect unknown.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

mild to moderate impairment (increased risk of

accumulation); avoid in severe impairment.

Dose adjustments Manufacturer advises dose reduction of

33% in mild to moderate impairment.

l RENAL IMPAIRMENT

Dose adjustments Manufacturers advise reduce daily dose

by half in moderate to severe renal impairment.

l EFFECT ON LABORATORY TESTS May interfere with

methacholine test—manufacturer advises stop treatment

96 hours prior to test. May interfere with skin testing for

allergy—manufacturer advises stop treatment one week

prior to test.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Drowsiness may affect

performance of skilled tasks (e.g. cycling or driving);

sedating effects enhanced by alcohol.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: oral suspension, oral

solution

Tablet

CAUTIONARY AND ADVISORY LABELS 2

▶ Hydroxyzine hydrochloride (Non-proprietary)

Hydroxyzine hydrochloride 10 mg Hydroxyzine 10mg tablets | 84 tablet P £1.20–£1.65 DT = £1.65

Hydroxyzine hydrochloride 25 mg Hydroxyzine 25mg tablets | 28 tablet P £0.62–£0.85 DT = £0.85

▶ Atarax (Alliance Pharmaceuticals Ltd)

Hydroxyzine hydrochloride 10 mg Atarax 10mg tablets |

84 tablet P £1.20 DT = £1.65

Hydroxyzine hydrochloride 25 mg Atarax 25mg tablets | 28 tablet P £0.62 DT = £0.85

Ketotifen

l INDICATIONS AND DOSE

Allergic rhinitis

▶ BY MOUTH

▶ Child 3–17 years: 1 mg twice daily

▶ Adult: 1 mg twice daily, increased if necessary to 2 mg

twice daily, to be taken with food

Allergic rhinitis in readily sedated patients

▶ BY MOUTH

▶ Adult: Initially 0.5–1 mg once daily, dose to be taken at

night

l CONTRA-INDICATIONS Avoid in Acute porphyrias p. 1058

l CAUTIONS Epilepsy . prostatic hypertrophy (in adults). pyloroduodenal obstruction . susceptibility to angleclosure glaucoma . urinary retention

l INTERACTIONS → Appendix 1: antihistamines, sedating

l SIDE-EFFECTS

▶ Common or very common Anxiety . insomnia . irritability

▶ Uncommon Cystitis . dizziness . dry mouth . skin reactions

▶ Rare or very rare Hepatitis . sedation . seizure . StevensJohnson syndrome . weight increased

SIDE-EFFECTS, FURTHER INFORMATION Drowsiness is a

significant side-effect with most of the older

antihistamines although paradoxical stimulation may

occur rarely, especially with high doses or in children and

the elderly. Drowsiness may diminish after a few days of

treatment and is considerably less of a problem with the

newer antihistamines.

l PREGNANCY Most manufacturers of antihistamines advise

avoiding their use during pregnancy; however, there is no

evidence of teratogenicity. Use in the latter part of the

third trimester may cause adverse effects in neonates such

as irritability, paradoxical excitability, and tremor.

l BREAST FEEDING Most antihistamines are present in

breast milk in varying amounts; although not known to be

harmful, most manufacturers advise avoiding their use in

mothers who are breast-feeding.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Drowsiness may affect

performance of skilled tasks (e.g. driving or cycling);

sedating effects enhanced by alcohol.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: oral solution

Oral solution

CAUTIONARY AND ADVISORY LABELS 2, 21

▶ Zaditen (CD Pharma Srl)

Ketotifen (as Ketotifen fumarate) 200 microgram per

1 ml Zaditen 1mg/5ml elixir sugar-free | 300 ml P £8.91 DT =

£8.91

Tablet

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