Solution for intravitreal injection, aflibercept 40 mg/mL, net price 0.1-mL vial = £816.00
PEGAPTANIB SODIUM
Indications see notes above — specialist use only
Cautions see notes above; also monitor intra-ocular pressure (transient increase may occur following injection, and small, sustained increases reported after repeated dosing); monitor for vitreous haemorrhage and for signs of ocular infection for 2 weeks following injection
Contra-indications ocular or periocular infection
Pregnancy manufacturer advises avoid unless potential benefit outweighs risk
Breast-feeding manufacturer advises avoid — no information available
Side-effects see notes above; also rhinorrhoea; headache; eye pain, anterior chamber inflammation, raised intra-ocular pressure, punctate keratitis, vitreous floaters, cataract, conjunctival and retinal haemorrhage, local oedema, conjunctivitis, corneal dystrophy, dry eye, eye discharge, eye irritation, macular degeneration, mydriasis, periorbital haematoma, photophobia, flashing lights, vitreous disorders; less commonly vomiting, dyspepsia, palpitation, chest pain, hypertension, aortic aneurysm, influenza-like symptoms, nightmares, depression, back pain, asthenopia, blepharitis, corneal deposits, vitreous haemorrhage, chalazion, retinal exudates, eyelid ptosis, decreased intra-ocular pressure, injection-site reactions, retinal detachment, occlusion of retinal blood vessels, ectropion, eye movement disorder, pupillary disorder, iritis, optic nerve cupping, nasopharyngitis, deafness, vertigo, eczema, changes in hair colour, rash, pruritus, night sweats
Dose
By intravitreal injection, ADULT over 18 years, 300 micrograms once every 6 weeks into the affected eye
Note For further information on administration, consult product literature. Review treatment if no benefit after 2 consecutive injections
NICE Technology Appraisal
NICE not recommended. See Ranibizumab and pegaptanib for the treatment of age-related macular degeneration (updated May 2012)
RANIBIZUMAB
Indications see notes above — specialist use only
Cautions see notes above; also history of stroke or transient ischaemic attack; patients at risk of retinal pigment epithelial tear; monitor intra-ocular pressure, perfusion of the optic nerve head, and for signs of ocular infection following injection; retinal detachment or macular hole — discontinue treatment if rhegmatogenous retinal detachment or stage 3 or 4 macular hole develops; diabetic macular oedema due to type 1 diabetes (limited information available); previous intravitreal injections; active systemic infection; proliferative diabetic retinopathy; uncontrolled hypertension; diabetic patients with HbA1c over 12%
Contra-indications ocular or periocular infection; severe intra-ocular inflammation; signs of irreversible ischaemic visual function loss in patients with retinal vein occlusion
Pregnancy manufacturer advises avoid unless potential benefit outweighs risk and recommends women use effective contraception during and for at least 3 months after treatment
Breast-feeding manufacturer advises avoid — no information available
Side-effects see notes above; also nausea, headache, nasopharyngitis, cough, anxiety, anaemia, urinary tract infection, arthralgia, raised intra-ocular pressure, visual disturbance, conjunctival, retinal, and vitreous disorders, ocular discomfort, eye haemorrhage, uveitis, iritis, blepharitis, iridocyclitis, cataract, posterior capsule opacification, punctuate keratitis, anterior chamber flare, conjunctivitis, photopsia, photophobia, eyelid oedema, allergic skin reactions; less commonly blindness, hypopyon, hyphaema, keratopathy, corneal disorders, iris adhesion
Dose
Neovascular (wet) age-related macular degeneration, by intravitreal injection, ADULT over 18 years, 500 micrograms once a month into the affected eye; monitor visual acuity monthly; continue treatment until visual acuity is stable for 3 consecutive months; thereafter monitor visual acuity monthly; if necessary subsequent doses may be given at least 1 month apart
Diabetic macular oedema, macular oedema secondary to retinal vein occlusion, by intravitreal injection, ADULT over 18 years, 500 micrograms once a month into the affected eye; monitor visual acuity monthly; continue treatment until visual acuity is stable for 3 consecutive months (discontinue treatment if no improvement in visual acuity after initial 3 injections); thereafter monitor visual acuity monthly; if necessary subsequent doses may be given at least 1 month apart
Choroidal neovascularisation secondary to pathologic myopia, by intravitreal injection, ADULT over 18 years, initially 500 micrograms as a single injection into the affected eye; monitor for disease activity monthly for first 2 months, then at least every 3 months thereafter during the first year, then as required; if necessary subsequent doses may be given at least 1 month apart
Concomitant treatment of diabetic macular oedema, or macular oedema secondary to branch retinal vein occlusion, with laser photocoagulation, by intravitreal injection, ADULT, 500 micrograms at least 30 minutes after laser photocoagulation
Note For further information on administration, consult product literature
NICE Technology Appraisals
NICE recommended. See Ranibizumab and pegaptanib for the treatment of age-related macular degeneration (updated May 2012)
NICE recommended. See Ranibizumab for the treatment of diabetic macular oedema (February 2013)
NICE recommended. See Ranibizumab for the treatment of visual impairment caused by macular oedema secondary to retinal vein occlusion (May 2013)
NICE recommended. See Ranibizumab for treating choroidal neovascularisation associated with pathological myopia (November 2013)
VERTEPORFIN
Indications see notes above — specialist use only
Cautions photosensitivity — avoid exposure of unprotected skin and eyes to bright light during infusion and for 48 hours afterwards; concomitant use with other photosensitising drugs; biliary obstruction; avoid extravasation
Contra-indications acute porphyria
Hepatic impairment use with caution in moderate impairment; avoid in severe impairment
Pregnancy manufacturer advises use only if potential benefit outweighs risk (teratogenic in animal studies)
Breast-feeding no information available — manufacturer advises avoid breast-feeding for 48 hours after administration
Side-effects nausea, hypercholesterolaemia, malaise, back pain, photosensitivity, visual disturbances (including reduced visual acuity, flashing lights, visual-field defects), less commonly hypertension, hyperaesthesia, pyrexia, retinal detachment, subretinal, retinal or vitreous haemorrhage, rarely retinal or choroidal vessel non-perfusion; also reported chest pain, myocardial infarction, vasovagal reactions, macular oedema, retinal oedema
Dose
By intravenous infusion over 10 minutes, 6 mg/m2
Note For information on administration and light activation, consult product literature
NICE Technology Appraisal
NICE recommended. See Verteporfin photodynamic therapy for wet age-related macular degeneration (September 2003)
Vitreomacular traction
Ocriplasmin is licensed for the treatment of vitreomacular traction, including when associated with a macular hole of diameter less than or equal to 400 microns. It is given by intravitreal injection by specialists experienced in the management of this condition.
The Scottish Medicines Consortium has advised (July 2014) that ocriplasmin (Jetrea®) is accepted for restricted use within NHS Scotland for the treatment of patients with vitreomacular traction plus macular hole, regardless of whether they have epiretinal membrane formation, and in patients with vitreomacular traction alone (no epiretinal membrane and no macular hole).
NICE guidance
Ocriplasmin for treating vitreomacular traction (October 2013)
Ocriplasmin is recommended as an option for treating vitreomacular traction in adults, only if:
an epiretinal membrane is not present and
they have a stage II full-thickness macular hole with a diameter of 400 microns or less and/or
they have severe symptoms.
OCRIPLASMIN
Indications see notes above — specialist use only
Cautions monitor intra-ocular pressure, visual acuity, and for signs of intra-ocular inflammation or infection following injection; non-proliferative diabetic retinopathy; history of uveitis (including severe active inflammation); significant eye trauma
Contra-indications active or suspected ocular or periocular infection; large diameter macular hole (> 400 microns); high myopia; aphakia; history of rhegmatogenous retinal detachment; lens zonule instability; recent ocular surgery or intra-ocular injection (including laser therapy); proliferative diabetic retinopathy; ischaemic retinopathies; retinal vein occlusions; exudative age-related macular degeneration; vitreous haemorrhage
Pregnancy manufacturer advises use only if potential benefit outweighs risk — no information available
Breast-feeding manufacturer advises use only if potential benefit outweighs risk — no information available
Side-effects conjunctival, retinal, and vitreous disorders, reduced visual acuity, raised intra-ocular pressure, macular hole, macular degeneration, macular oedema, metamorphopsia, eyelid oedema, anterior chamber cell or flare, iritis, photopsia, ocular hyperaemia, abnormal retinograph, ocular discomfort, photophobia, chromatopsia, retinal pigment epitheliopathy; less commonly transient blindness, lens subluxation, scotoma, visual field defect, diplopia, hyphaema, miosis, unequal pupils, corneal abrasion, anterior chamber inflammation, eye inflammation
Dose
By intravitreal injection, ADULT over 18 years, 125 micrograms as a single dose into the affected eye
Note Concurrent administration to both eyes not recommended. For further information on administration, consult product literature
NICE Technology Appraisal
NICE recommended. See Ocriplasmin for treating vitreomacular traction (October 2013)
11.9 Contact lenses
For cosmetic reasons many people prefer to wear contact lenses rather than spectacles; contact lenses are also sometimes required for medical indications. Visual defects are corrected by either rigid (‘hard’ or gas permeable) lenses or soft (hydrogel or silicone hydrogel) lenses; soft lenses are the most popular type, because they are initially the most comfortable, but they may not give the best vision. Lenses should usually be worn for a specified number of hours each day and removed for sleeping. The risk of infectious and non-infectious keratitis is increased by extended continuous contact lens wear, which is not recommended, except when medically indicated.
Contact lenses require meticulous care. Poor compliance with directions for use, and with daily cleaning and disinfection, can result in complications including ulcerative keratitis or conjunctivitis. One-day disposable lenses, which are worn only once and therefore require no disinfection or cleaning, are becoming increasingly popular.
Acanthamoeba keratitis, a painful and sight-threatening condition, is associated with ineffective lens cleaning and disinfection, the use of contaminated lens cases, or tap water coming into contact with the lenses. The condition is especially associated with the use of soft lenses (including frequently replaced lenses) and should be treated by specialists.
Contact lenses and drug treatment Special care is required in prescribing eye preparations for contact lens users. Some drugs and preservatives in eye preparations can accumulate in hydrogel lenses and may induce toxic reactions. Therefore, unless medically indicated, the lenses should be removed before instillation of the eye preparation and not worn during the period of treatment. Alternatively, unpreserved drops can be used. Eye drops may, however, be instilled while patients are wearing rigid corneal contact lenses. Ointment preparations should never be used in conjunction with contact lens wear; oily eye drops should also be avoided.
Many drugs given systemically can also have adverse effects on contact lens wear. These include oral contraceptives (particularly those with a higher oestrogen content), drugs which reduce blink rate (e.g. anxiolytics, hypnotics, antihistamines, and muscle relaxants), drugs which reduce lacrimation (e.g. antihistamines, antimuscarinics, phenothiazines and related drugs, some beta-blockers, diuretics, and tricyclic antidepressants), and drugs which increase lacrimation (including ephedrine and hydralazine). Other drugs that may affect contact lens wear are isotretinoin (can cause conjunctival inflammation), aspirin (salicylic acid appears in tears and can be absorbed by contact lenses — leading to irritation), and rifampicin and sulfasalazine (can discolour lenses).
12 Ear, nose, and oropharynx
This chapter also includes advice on the drug management of the following:
12.1 Drugs acting on the ear
12.1.1 Otitis externa
Otitis externa is an inflammatory reaction of the meatal skin. It is important to exclude an underlying chronic otitis media before treatment is commenced. Many cases recover after thorough cleansing of the external ear canal by suction or dry mopping. A frequent problem in resistant cases is the difficulty in applying lotions and ointments satisfactorily to the relatively inaccessible affected skin. The most effective method is to introduce a ribbon gauze dressing or sponge wick soaked with corticosteroid ear drops or with an astringent such as aluminium acetate solution. When this is not practical, the ear should be gently cleansed with a probe covered in cotton wool and the patient encouraged to lie with the affected ear uppermost for ten minutes after the canal has been filled with a liberal quantity of the appropriate solution.
If infection is present, a topical anti-infective which is not used systemically (such as neomycin or clioquinol) may be used, but for only about a week as excessive use may result in fungal infections; these may be difficult to treat and require expert advice. Sensitivity to the anti-infective or solvent may occur and resistance to antibacterials is a possibility with prolonged use. Aluminium acetate ear drops are also effective against bacterial infection and inflammation of the ear. Chloramphenicol may be used but the ear drops contain propylene glycol and cause hypersensitivity reactions in about 10% of patients. Solutions containing an anti-infective and a corticosteroid (such as Locorten-Vioform®) are used for treating cases where infection is present with inflammation and eczema.
In view of reports of ototoxicity, manufacturers contra-indicate treatment with topical aminoglycosides or polymyxins in patients with a perforated tympanic membrane (eardrum) or patent grommet. However, some specialists do use these drops cautiously in the presence of a perforation or patent grommet in patients with chronic suppurative otitis media (section 12.1.2) and when other measures have failed for otitis externa; treatment should be considered only by specialists in the following circumstance:
drops should only be used in the presence of obvious infection;
treatment should be for no longer than 2 weeks;
patients should be counselled on the risk of ototoxicity and given justification for the use of these topical antibiotics;
baseline audiometry should be performed, if possible, before treatment is commenced.
Clinical expertise and judgement should be used to assess the risk of treatment versus the benefit to the patient in such circumstances.
A solution of acetic acid 2% acts as an antifungal and antibacterial in the external ear canal. It may be used to treat mild otitis externa but in severe cases an anti-inflammatory preparation with or without an anti-infective drug is required. A proprietary preparation containing acetic acid 2% (EarCalm® spray) is on sale to the public.
For severe pain associated with otitis externa, a simple analgesic, such as paracetamol (section 4.7.1) or ibuprofen (section 10.1.1), can be used. A systemic antibacterial (Table 1, section 5.1) can be used if there is spreading cellulitis or if the patient is systemically unwell. When a resistant staphylococcal infection (a boil) is present in the external auditory meatus, flucloxacillin is the drug of choice; ciprofloxacin (or an aminoglycoside) may be needed in pseudomonal infections which may occur if the patient has diabetes or is immunocompromised.
The skin of the pinna adjacent to the ear canal is often affected by eczema. Topical corticosteroid creams and ointments (section 13.4) are then required, but prolonged use should be avoided.
Astringent preparations
ALUMINIUM ACETATE
Indications inflammation in otitis externa (see notes above)
Dose
Insert into meatus or apply on a ribbon gauze dressing or sponge wick which should be kept saturated with the ear drops
Aluminium Acetate (Non-proprietary)
Ear drops 13%, aluminium sulfate 2.25 g, calcium carbonate 1 g, tartaric acid 450 mg, acetic acid (33%) 2.5 mL, purified water 7.5 mL
Available from manufacturers of ‘special order’ products
Ear drops 8%, dilute 8 parts aluminium acetate ear drops (13%) with 5 parts purified water. Must be freshly prepared
Anti-inflammatory preparations
Corticosteroids
Topical corticosteroids are used to treat inflammation and eczema in otitis externa.
Cautions Prolonged use of topical corticosteroid ear preparations should be avoided.
Contra-indications Corticosteroid ear preparations should be avoided in the presence of an untreated ear infection. If infection is present, the corticosteroid should be used in combination with a suitable anti-infective (see notes above).
Side-effects Local sensitivity reactions may occur.
BETAMETHASONE SODIUM PHOSPHATE
Indications eczematous inflammation in otitis externa (see notes above)
Cautions see notes above
Contra-indications see notes above
Side-effects see notes above
Betnesol® (RPH) 
Drops (for ear, eye, or nose), betamethasone sodium phosphate 0.1%. Net price 10 mL = £2.32
Excipients include benzalkonium chloride, disodium edetate
Dose ear, apply 2–3 drops every 2–3 hours; reduce frequency when relief obtained; eye, section 11.4.1; nose, section 12.2.1
Vistamethasone® (Martindale) 
Drops (for ear, eye, or nose), betamethasone sodium phosphate 0.1%. Net price 5 mL = £1.02; 10 mL = £1.16
Excipients include benzalkonium chloride, disodium edetate
Dose ear, apply 2–3 drops every 3–4 hours; reduce frequency when relief obtained; eye, section 11.4.1; nose, section 12.2.1
With antibacterial
Betnesol-N® (RPH) 
Drops (for ear, eye, or nose), betamethasone sodium phosphate 0.1%, neomycin sulfate 0.5%. Net price 10 mL = £2.39
Excipients include benzalkonium chloride, disodium edetate
Dose ear, apply 2–3 drops 3–4 times daily; eye, section 11.4.1; nose, section 12.2.3
DEXAMETHASONE
Indications eczematous inflammation in otitis externa (see notes above)
Cautions see notes above
Contra-indications see notes above
Side-effects see notes above
With antibacterial
Otomize® (Forest) 
Ear spray, dexamethasone 0.1%, neomycin sulfate 3250 units/mL, glacial acetic acid 2%. Net price 5-mL pump-action aerosol unit = £3.27
Excipients include hydroxybenzoates (parabens)
Dose ADULT and CHILD over 2 years, apply 1 metered spray 3 times daily
Sofradex® (Sanofi-Aventis) 
Drops (for ear or eye), dexamethasone (as sodium metasulphobenzoate) 0.05%, framycetin sulfate 0.5%, gramicidin 0.005%. Net price 10 mL = £6.25
Excipients include polysorbate 80
Dose ear, apply 2–3 drops 3–4 times daily; eye, section 11.4.1
FLUMETASONE PIVALATE
(Flumethasone Pivalate)
Indications eczematous inflammation in otitis externa (see notes above)
Cautions see notes above
Contra-indications see notes above
Side-effects see notes above
HYDROCORTISONE
Indications eczematous inflammation in otitis externa (see notes above)
Cautions see notes above
Contra-indications see notes above
Side-effects see notes above
PREDNISOLONE SODIUM PHOSPHATE
Indications eczematous inflammation in otitis externa (see notes above)
Cautions see notes above
Contra-indications see notes above
Side-effects see notes above
Predsol® (RPH) 
Drops (for ear or eye), prednisolone sodium phosphate 0.5%. Net price 10 mL = £2.00
Excipients include benzalkonium chloride, disodium edetate
Dose ear, apply 2–3 drops every 2–3 hours; reduce frequency when relief obtained; eye, section 11.4.1
Anti-infective preparations
CHLORAMPHENICOL 
Indications bacterial infection in otitis externa (but see notes above)
Cautions avoid prolonged use (see notes above)
Side-effects high incidence of sensitivity reactions to vehicle
Chloramphenicol (Non-proprietary) 
Ear drops, chloramphenicol in propylene glycol, net price 5%, 10 mL = £40.92; 10%, 10 mL = £19.52
Dose ear, apply 2–3 drops 2–3 times daily
CLIOQUINOL
Indications mild bacterial or fungal infections in otitis externa (see notes above)
Cautions avoid prolonged use (see notes above); manufacturer advises avoid in perforated tympanic membrane (but used by specialists for short periods)
Side-effects local sensitivity; stains skin and clothing
CLOTRIMAZOLE
Indications fungal infection in otitis externa (see notes above)
Side-effects occasional local irritation or sensitivity
Canesten® (Bayer Consumer Care)
Solution, clotrimazole 1% in polyethylene glycol 400 (macrogol 400). Net price 20 mL = £2.30
Dose ear, apply 2–3 times daily continuing for at least 14 days after disappearance of infection; skin, section 13.10.2
FRAMYCETIN SULFATE
Indications bacterial infection in otitis externa (see notes above)
Cautions avoid prolonged use (see notes above)
Contra-indications perforated tympanic membrane (see notes above)
Side-effects local sensitivity
GENTAMICIN
Indications bacterial infection in otitis externa (see notes above)
Cautions avoid prolonged use (see notes above)
Contra-indications perforated tympanic membrane (but see also notes above and section 12.1.2)
Side-effects local sensitivity
Genticin® (AMCo) 
Drops (for ear or eye), gentamicin 0.3% (as sulfate). Net price 10 mL = £2.13
Excipients include benzalkonium chloride
Dose ear, apply 2–3 drops 3–4 times daily and at night; eye, section 11.3.1
NEOMYCIN SULFATE
Indications bacterial infection in otitis externa (see notes above)
Cautions avoid prolonged use (see notes above)
Contra-indications perforated tympanic membrane (see notes above)
Side-effects local sensitivity
12.1.2 Otitis media
Acute otitis media Acute otitis media is the commonest cause of severe aural pain in small children. Many infections, especially those accompanying coryza, are caused by viruses. Most uncomplicated cases resolve without antibacterial treatment and a simple analgesic, such as paracetamol, may be sufficient. In children without systemic features, a systemic antibacterial (Table 1, section 5.1) may be started after 72 hours if there is no improvement, or earlier if there is deterioration, if the patient is systemically unwell, if the patient is at high risk of serious complications (e.g. in immunosuppression, cystic fibrosis), if mastoiditis is present, or in children under 2 years of age with bilateral otitis media. Perforation of the tympanic membrane in patients with acute otitis media usually heals spontaneously without treatment; if there is no improvement, e.g. pain or discharge persists, a systemic antibacterial (Table 1, section 5.1) can be given. Topical treatment of acute otitis media is ineffective and there is no place for drops containing a local anaesthetic.
Otitis media with effusion Otitis media with effusion (glue ear) occurs in about 10% of children and in 90% of children with cleft palates. Systemic antibacterials are not usually required. If glue ear persists for more than a month or two, the child should be referred for assessment and follow up because of the risk of long-term hearing impairment which can delay language development. Untreated or resistant glue ear may be responsible for some types of chronic otitis media.
Chronic otitis media Opportunistic organisms are often present in the debris, keratin, and necrotic bone of the middle ear and mastoid in patients with chronic otitis media. The mainstay of treatment is thorough cleansing with aural microsuction which may completely resolve long-standing infection. Local cleansing of the meatal and middle ear may be followed by treatment with a sponge wick or ribbon gauze dressing soaked with corticosteroid ear drops or with an astringent such as aluminium acetate solution; this is particularly beneficial for discharging ears or infections of the mastoid cavity. An antibacterial ear ointment may also be used. Acute exacerbations of chronic infection may also require systemic treatment with amoxicillin (or erythromycin if penicillin-allergic); treatment is adjusted according to the results of sensitivity testing.
In view of reports of ototoxicity, manufacturers contra-indicate topical treatment with ototoxic antibacterials in the presence of a tympanic perforation or patent grommet. Ciprofloxacin or ofloxacin eye drops used in the ear [unlicensed use] or ear drops [both unlicensed; available from ‘special-order’ manufacturers or specialist importing companies] are an effective alternative to such ototoxic ear drops for chronic otitis media in patients with perforation of the tympanic membrane.
However, some specialists do use ear drops containing aminoglycosides or polymyxins [unlicensed indications] cautiously in patients with chronic suppurative otitis media and a perforation of the tympanic membrane, if the otitis media has failed to settle with systemic antibacterials; treatment should be considered only by specialists in the following circumstance:
drops should only be used in the presence of obvious infection;
treatment should be for no longer than 2 weeks;
patients should be counselled on the risk of ototoxicity and given justification for the use of these topical antibiotics;
baseline audiometry should be performed, if possible, before treatment is commenced.
Clinical expertise and judgement should be used to assess the risk of treatment versus the benefit to the patient in such circumstances. It is considered that the pus in the middle ear associated with otitis media also carries a risk of ototoxicity.
12.1.3 Removal of ear wax
Wax is a normal bodily secretion which provides a protective film on the meatal skin and need only be removed if it causes hearing loss or interferes with a proper view of the ear drum.
Wax can be softened using simple remedies such as olive oil ear drops or almond oil ear drops; sodium bicarbonate ear drops are also effective, but may cause dryness of the ear canal. If the wax is hard and impacted, the drops can be used twice daily for several days and this may reduce the need for mechanical removal of the wax. The patient should lie with the affected ear uppermost for 5 to 10 minutes after a generous amount of the softening remedy has been introduced into the ear. Some proprietary preparations containing organic solvents can irritate the meatal skin, and in most cases the simple remedies indicated above are just as effective and less likely to cause irritation. Docusate sodium or urea–hydrogen peroxide are ingredients in a number of proprietary preparations for softening ear wax.
If necessary, wax may be removed by irrigation with water (warmed to body temperature). Ear irrigation is generally best avoided in young children, in patients unable to co-operate with the procedure, in those with otitis media in the last six weeks, in otitis externa, in patients with cleft palate, a history of ear drum perforation, or previous ear surgery. A person who has hearing in one ear only should not have that ear irrigated because even a very slight risk of damage is unacceptable in this situation.
Almond Oil (Non-proprietary)
Ear drops, almond oil in a suitable container
Allow to warm to room temperature before use
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