Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• For pruritus, offer a sedating antihistamine e.g. chlorphenamine or hydroxyzine, to be taken at bedtime.

• There is very limited evidence that antihistamines are effective in treating pruritus.
• Chlorphenamine and hydroxyzine are sedating oral antihistamines. They probably provide a reprieve from nocturnal scratching by causing sedation, helping to break the itch-scratch-itch cycle:
• Hydroxyzine is specifically licensed for pruritus.
• Chlorphenamine (chlorphenamine) is inexpensive, and is an effective sedating antihistamine of intermediate duration.
• Alimemazine (licensed for pruritus) and promethazine (not licensed for pruritus) have pronounced sedative effects. Hangover effects are common and these drugs are therefore not recommended.
• A review of 16 randomized controlled trials and other studies (n = 803) suggests that neither first nor second generation antihistamines offer relief from itch in conditions such as atopic dermatitis [Klein and Clark, 1999].
• Several small, poorly designed trials have found that loratadine and cetirizine reduce cutaneous reactions and pruritus when given for mosquito bites. However, larger studies are needed to confirm this [Karppinen et al, 2000; Karppinen et al, 2002].

• Cetirizine, fexofenadine, or loratadine (once-daily non-sedating antihistamines) are recommended for the treatment of urticaria.
• If an additional sedating antihistamine is needed for night-time use, if the itch is interfering with sleep, chlorphenamine or hydroxyzine are recommended.

• Non-sedating antihistamines are routinely increased beyond the recommended licensed dose in secondary care to control symptoms. It is not advisable to increase above the maximum licensed dose unless the healthcare professional has experience in doing so, or before seeking specialist advice.

• Antihistamines (H₁-receptor blockers) are the only drugs licensed for use in urticaria.
• Although the efficacy of antihistamines has only been demonstrated for chronic urticaria, there is a consensus that they are also effective for acute urticaria [Grattan et al, 2001; Zuberbier et al, 2006]:
• Histamine is one of the primary mediators of urticaria.
• In people with chronic urticaria, randomized controlled trials of non-sedating antihistamines have demonstrated improvements in symptoms of itch, weal formation, frequency of exacerbations, and quality of life [Belaich et al, 1990; Breneman et al, 1995; Kaplan et al, 2005; Zuberbier et al, 2006].
• Non-sedating antihistamines should therefore be used initially to control daytime symptoms.
• Sedating antihistamines are not recommended for daytime use because the drowsiness they cause can affect a person's ability to drive or perform other skilled tasks [Grattan et al, 2001; Zuberbier et al, 2006]. However, the addition of a sedating antihistamine at night to a non-sedating (daytime) antihistamine may help people who are unable to sleep due to itching, and is considered to be safe [Grattan et al, 2001].
• Desloratadine (a metabolite of loratadine) and levocetirizine (an isomer of cetirizine) are more recently marketed products, but there is little evidence to confirm whether they confer any additional benefit over the more established non-sedating antihistamines [MeReC, 2004].
• Mizolastine has been implicated in causing an abnormal prolongation of the QT interval and is therefore not recommended as a first-line treatment.
• Acrivastine is not recommended as it has a short half-life and needs to be taken three times a day.

• Sedating antihistamines cause sedation in 10–50% of people, which can persist into the next day [DTB, 2002].
• Most non-sedating antihistamines have the potential to cause sedation, especially at higher doses. Advise people taking non-sedating antihistamines that they may cause sedation, and that the sedative effects are enhanced when combined with alcohol.

• Where possible, oral antihistamines should be avoided during pregnancy, especially during the first trimester.
• If an oral antihistamine is required to control urticaria or pruritus during pregnancy, chlorphenamine is the antihistamine of choice.

• Topical corticosteroids are associated with localized effects, such as skin atrophy and exacerbation of skin infections (e.g. fungal infection):
• The risk of adverse effects increases with the potency of the topical corticosteroid, duration of use, and area of application (e.g. thin skin on the genitalia). Adverse effects are most likely with potent or super-potent topical corticosteroids when used in large quantities for prolonged periods.
• Mildly and moderately potent topical corticosteroids used for short periods are rarely associated with adverse effects.
• Skin atrophy is much more likely with potent and very potent topical corticosteroids.
• There is little risk of skin thinning with mildly to moderately potent topical corticosteroids when used for up to 4 weeks.
• Contact allergy to topical corticosteroids has also been reported (4–5%). The allergy is normally to preservatives in the preparation (more likely with creams) or, more rarely, to the corticosteroid itself.
• Note: systemic effects, such as hypophyseal-pituitary-adrenal (HPA) suppression which may lead to growth retardation, are extremely rare. HPA has been observed following prolonged application of potent steroids to large areas of skin.

[MeReC, 1999; DTB, 2003]

• Adverse effects are uncommon with occasional, short courses of oral corticosteroids.
• If frequent courses of oral corticosteroids are needed, the following monitoring is recommended:
• People taking frequent courses of oral corticosteroids require specialist supervision.
• Blood pressure: monitor regularly and treat if necessary.
• Diabetes mellitus: screen regularly and treat if necessary.
• Osteoporosis: see the CKS topic on Osteoporosis - preventing steroid-induced for details about when to prescribe long-acting bisphosphonate therapy.
• Growth suppression: record height of children regularly and accurately.
• Cataracts: screen children periodically.
• Children who are on frequent courses of oral corticosteroids should have regular checks for signs of adrenal suppression, with referral to a paediatrician who can arrange synacthen testing where appropriate.

• Anyone with a history of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins) or excipients.
• Anyone with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.

[ABPI Medicines Compendium, 2008a]

• Diarrhoea is a common adverse effect of flucloxacillin.
• Cholestatic jaundice and hepatitis may occur (very rarely) up to several weeks after treatment with flucloxacillin has been stopped. Administration for more than 2 weeks, and increasing age, are risk factors [CSM, 2004].
• Allergic reactions which cause rashes and anaphylaxis can occur in 1–10% of people treated with penicillins [BNF 52, 2006].

• People taking astemizole, pimozide, ergotamine, or dihydroergotamine should avoid taking erythromycin [BNF 52, 2006].

• Erythromycin commonly causes gastrointestinal adverse effects, especially at higher doses. If gastrointestinal adverse effects are known to occur, consider prescribing clarithromycin instead.
• Cardiac arrhythmias have been very rarely reported in people taking erythromycin or clarithromycin.

[ABPI Medicines Compendium, 2002]