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).

• If practical, have someone other than the patient administer the treatment.
• If there is substantial exudate, remove this by gentle (atraumatic) dry swabbing using a cotton bud or twist of cotton wool.
• Warm the drops up to body temperature by holding the bottle in hands or pocket for a few minutes — this prevents the dizziness that can occur if cold drops are administered.
• To administer the ear drops to ensure optimal delivery throughout the external ear canal:
• The person should lie down with the ear to be treated uppermost.
• The ear canal should be filled with ear drops. Gently pulling and pushing the ear helps to let air out of, and liquid into, the ear canal.
• The person should remain in this position for 3–5 minutes. A kitchen timer may be useful to get young children to cooperate.
• If the person (e.g. a small child) cannot lie still long enough to allow absorption, a small cotton plug covered with petroleum jelly or moistened with the drops and placed at the external opening of the ear canal for about 5 minutes can be used to help retain the drops in the ear.
• A small cotton swab placed at the tragus can be used to catch any leakage from the ear when sitting up.
• The ear canal should be left open to dry.

• These are pragmatic recommendations largely based on expert opinion [Sander, 2001; American Academy of Otolaryngology et al, 2006].
• The recommendation that ear drops be warmed up to body temperature is to prevent nystagmus, dizziness, and vertigo from the equivalent of a caloric stimulation test of the auditory nerve [Sander, 2001].
• The recommendation that someone else administer the ear drops if practical is based on evidence that up to 60% of people self-administering ear drops do not do this adequately for the first 3 days of treatment [American Academy of Otolaryngology et al, 2006].

• People with (or history of) a local sensitivity reaction should avoid preparations with the same class of drug associated with the reaction. For example, if neomycin is thought to have caused a sensitivity reaction all preparations containing aminoglycosides should be avoided.
• People who have a perforated tympanic membrane should avoid topical aminoglycosides.

• Sensitivity reactions:
• Prolonged or recurrent use of topical preparations can result in sensitization of the auricle or external auditory canal, leading to an allergic reaction (secondary contact otitis) [Sood et al, 2002].
• This reaction can be caused by the drug itself or excipients found in the vehicle (see Table 1).
• The aminoglycoside, neomycin, is the most common substance in topical ear preparations causing sensitization [Sood et al, 2002; American Academy of Otolaryngology et al, 2006].
• Neomycin has been reported to cause reactions in about 5–15% of patients with chronic external otitis [American Academy of Otolaryngology et al, 2006].
• There are significant cross-reactions with framycetin and gentamicin [Sood et al, 2002].
• Ototoxicity with aminoglycoside antibiotics:
• The Committee on Safety of Medicines (CSM) advises that topical ear canal treatment with aminoglycosides is contraindicated in people with a tympanic perforation [CSM, 1997].
• For further information, see Adverse effects and harms of treatments.

• Flucloxacillin should not be used in patients with a history of flucloxacillin-associated jaundice or hepatic dysfunction [CSM, 2004].
• Flucloxacillin should be used with caution in people with hepatic dysfunction [CSM, 2004].

• The Committee on Safety of Medicines (CSM) warns that [CSM, 1992; CSM, 2004]:
• Flucloxacillin has been (rarely) associated with hepatitis and cholestatic jaundice.
• The onset of hepatic reactions may be delayed for several weeks (up to 2 months) after treatment with flucloxacillin has ceased.
• These reactions are related neither to the dose nor to the route of administration of flucloxacillin. Risk factors include treatment for more than 2 weeks, and increasing age.
• Careful enquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.

• People who have had intolerable gastrointestinal effects from erythromycin:
• Consider prescribing prescribing clarithromycin.
• People taking drugs metabolized by cytochrome P450 isoenzymes (e.g. theophylline, carbamazepine, digoxin, warfarin) [Aronson, 2006]:
• The effects of these drugs may be increased because erythromycin and clarithromycin inhibit cytochrome P450 isoenzymes.
• An additional concern is that broad spectrum antibiotics can reduce the number of bacteria in the gut that produce vitamin K, and thus potentiate the effects of warfarin.
• People taking drugs that can prolong the QT interval (e.g. antiarrhythmics, antipsychotics, tricyclic antidepressants), and people with hypokalaemia:
• Macrolides also prolong the QT interval, and therefore should, if possible, not be used together with these drugs.
• Macrolides should not be used in people with hypokalaemia, which also increases the risk of QT prolongation.
• People taking statins:
• The risk of myopathy and rhabdomyolysis is increased, as macrolides can inhibit the metabolism of statins [Aronson, 2006].
• For more information on drug interactions with macrolides, see the British National Formulary [BNF 53, 2007].