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).

Note: eye drops containing preservatives, particularly benzalkonium chloride, accumulate in soft contact lenses and can cause irritation. Therefore soft contact lenses should not be worn during treatment period.

• Azelastine, emedastine, or ketotifen, and antazoline combined with a sympathomimetic — xylometazoline (Otrivine-Antistin^®) — are recommended for the symptomatic treatment of allergic conjunctivitis.
• Emedastine and ketotifen are licensed for use in adults and in children from 3 years of age onwards, azelastine from 4 years of age onwards, and Otrivine-Antistin^® from 12 years of age onwards.
• Azelastine and Otrivine-Antistin^® (for adults and children over 12 years of age) can be purchased over the counter for the treatment of seasonal and perennial allergic conjunctivitis.

• Azelastine is licensed for the symptomatic treatment of seasonal and perennial allergic conjunctivitis, and emedastine and ketotifen are licensed for the symptomatic treatment of seasonal allergic conjunctivitis.
• With the combination product Otrivine-Antistin^®, the antazoline antihistamine component relieves itchiness and other allergic symptoms whilst the xylometazoline component acts as a vasoconstrictor and rapidly relieves the associated redness [Bielory et al, 2005].
• Epinastine and olopatidine are also licensed for the symptomatic treatment of seasonal allergic conjunctivitis, but they are black triangle drugs and therefore remain under the surveillance of the Commission on Human Medicines (formerly Committee on Safety of Medicines) [BNF 53, 2007]. In addition, epinastine is only licensed to be used for a maximum of 8 weeks and olopatidine is only licensed to be used for a maximum of 4 months [ABPI Medicines Compendium, 2007b; ABPI Medicines Compendium, 2007c].

• Topical ocular antihistamines are not recommended for use in pregnancy or breastfeeding, as their safety in these scenarios has not been established.
• For oral antihistamines that can be used in pregnancy and breastfeeding, see the section on oral antihistamines In pregnancy and breastfeeding.

• In the unlikely event that topical ocular antihistamines cause transient changes in vision, advise the person to wait until these changes resolve before driving or performing other skilled tasks such as operating machinery.
• Azelastine — occasionally mild transient irritation is experienced [ABPI Medicines Compendium, 2006].
• Emedastine — the most common ocular adverse reaction is discomfort in the form of transient burning or stinging upon instillation [ABPI Medicines Compendium, 2002a].
• Ketotifen — eye irritation, burning or stinging, and punctate corneal epithelial erosion are the most commonly reported adverse effects [ABPI Medicines Compendium, 2007a].
• Antazoline/xylometazoline (Otrivine-Antistin^®) combination — should only be used short term, as overuse of vasoconstrictors may lead to rebound hyperaemia, irritation, and systemic adverse effects [Bielory et al, 2005]. Otrivine-Antistin^® should be used with caution in people susceptible to close-angle glaucoma, as prolonged use can increase intraocular pressure and precipitate glaucoma [BNF 53, 2007].

• Cetirizine, fexofenadine, or loratadine (once-daily non-sedating antihistamines) is recommended for the symptomatic treatment of allergic conjunctivitis.

• CKS does not recommend sedating antihistamines for allergic conjunctivitis because the drowsiness they cause can affect a person's ability to drive or perform other skilled tasks and several other options are available [BNF 53, 2007].
• 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 because it needs to be taken three times daily and is therefore less desirable from a patient compliance perspective.

• Where possible, oral antihistamines should be avoided during pregnancy, especially during the first trimester.
• During pregnancy — a topical ocular antihistamine is probably safe as minimal systemic exposure can be expected, or alternatively an 'older sedating' antihistamine such as oral chlorphenamine is recommended.
• During breastfeeding — oral loratadine or oral cetirizine can be recommended.

[Lee et al, 2000; DTB, 2002; NTIS, 2002; UKMiCentral, 2004]

• Chlorphenamine is not licensed during pregnancy, but there have been several thousand known exposures to this during pregnancy, with no evidence of an increased risk of fetal toxicity.
• The safety of other oral antihistamines in pregnancy has not been established. The available evidence does not suggest that other antihistamines (sedating or non-sedating) are associated with a high risk of teratogenic effects, but not enough exposures have been documented to be confident that there is no or minimal risk of fetal malformations.
• Loratadine and cetirizine are preferred during breastfeeding because only small amounts are secreted in breast milk and both drugs are non-sedating.

[Lee et al, 2000; DTB, 2002; NTIS, 2002; UKMiCentral, 2004]

• Most non-sedating antihistamines can cause sedation, especially at higher doses, because they penetrate the blood–brain barrier (although to a much lesser extent than sedating antihistamines) [DTB, 2002]. Advise people taking non-sedating antihistamines that they may cause sedation and therefore may affect ability to drive, and that the sedative effects are enhanced when combined with alcohol.

Note: eye drops containing preservatives, particularly benzalkonium chloride, accumulate in soft contact lenses and can cause irritation. Therefore soft contact lenses should not be worn during treatment period.

• Lodoxamide, nedocromil sodium, or sodium cromoglicate is recommended for prophylaxis of allergic conjunctivitis.
• Lodoxamide is licensed for use in adults and children from 4 years of age onwards, nedocromil sodium from 6 years of age onwards, and sodium cromoglicate from 1 year of age onwards.
• Lodoxamide (for adults and children over 4 years of age) and sodium cromoglicate (for adults and children over 6 years of age) can be purchased over the counter for the treatment of allergic conjunctivitis.

[ABPI Medicines Compendium, 2002b; ABPI Medicines Compendium, 2004a; ABPI Medicines Compendium, 2004b]

• In the unlikely event that the use of a topical ocular mast cell stabilizer causes transient vision changes, advise the person to wait until these changes resolve before driving or operating machinery.
• Lodoxamide — the most frequently reported ocular adverse effects are transient burning, stinging, or discomfort upon instillation, which occur in 13% of people using the eye drops [ABPI Medicines Compendium, 2002b].
• Transient stinging and burning may also occur after instillation of nedocromil sodium or sodium cromoglicate [ABPI Medicines Compendium, 2004a; ABPI Medicines Compendium, 2004b].
• An unpleasant taste immediately after instillation of nedocromil sodium eye drops has been reported [Wormald et al, 2004].

• Lodoxamide [ABPI Medicines Compendium, 2002b]:
• Should be used during pregnancy only if clearly needed.
• Use caution when administering lodoxamide to nursing mothers, as it is not known whether lodoxamide is secreted in human milk.
• Nedocromil sodium — use with caution during pregnancy (especially during the first trimester) and whilst breastfeeding [ABPI Medicines Compendium, 2004a].
• Sodium cromoglicate [ABPI Medicines Compendium, 2004b]:
• Should be used in pregnancy only where there is a clear need.
• No information suggests that sodium cromoglicate is harmful in breastfeeding.

• An oral corticosteroid should normally be taken as a single dose in the morning to reduce the disturbance to circadian cortisol secretion [BNF 53, 2007].
• Adverse effects are uncommon with occasional, short courses of oral corticosteroids.
• When prescribing a corticosteroid, be aware of other corticosteroids formulations (e.g. creams, ointments, inhalers) being used by the person as the potential for adverse effects is increased.
• If frequent courses of oral corticosteroids are needed, refer to an immunologist for further assessment and management.