New Medicines Committee Briefing November 2013
Topical Corticosteroids
Topical corticosteroids are to be reviewed for use within: Primary Care
Secondary Care
Formulary application:
Consultant submitting application: Dr Nicholas Craven (Consultant Dermatologist) Clinical Director supporting application: Mr Gareth Rowland
Dr Craven has requested that the whole skin section of the formulation be reviewed. As part of this process, the topical corticosteroid section is being reviewed. Dr Craven has requested that fluocinolone acetonide 0.0025% cream, fluocinolone acetonide 0.00625% cream and ointment, fluocinolone acetonide 0.025% cream, gel and ointment, fluocinolone acetonide 0.025% with clioquinol 3% cream and ointment, fluocinolone acetonide 0.025% with neomycin 0.5% cream and ointment, Haelan® tape, Trimovate® cream, Diprosalic® ointment and Nerisone Forte® oily cream and ointment be included in the North Staffordshire Joint Formulary while the following corticosteroids: hydrocortisone 0.5% cream and ointment 30g, hydrocortisone 1% cream and ointment 50g, hydrocortisone 2.5% cream and ointment, Canesten HC® cream 15g, Daktacort® cream 15g, Fucidin H® cream 60g, Betnovate® scalp application, Fucibet® cream 60g, and Clarelux® Foam Scalp Application) be removed from the Joint Formulary. Dr Craven states that Haelan® tape would be used in the following conditions: nodular prurigo, lichen simplex, fissured dermatitis, stubborn plaques of psoriasis, chronic discoid lupus erythematosus and granuloma annulare, plus any other stubborn localised steroid-responsive dermatoses. The super-potent topical steroids such as Dermovate® and Nerisone Forte® are used when the affected areas are more extensive. He also stated that the Synalar® products will be used in patients allergic to hydrocortisone, clobetasone butyrate and betamethasone esters and that Synalar gel is standard treatment for steroid-responsive dermatoses in the scalp. 1
He noted that these are well-established products which should be available in any dermatological formulary. A healthy selection of topical corticosteroids ranging from mild to very potent, with or without antimicrobials, are essential as there is wide inter-patient variability in response to treatments.
Relevance in therapy:
Corticosteroids are synthetic analogues of the natural hormones that are produced by the adrenal cortex. Like the natural hormones, synthetic corticosteroids can have glucocorticoid and/or mineralocorticoid properties. Corticosteroids can be administered systemically (orally and parenterally) or locally (topically to the skin, nose, and eyes; by inhalation; rectally and by intra- articular injection). Local corticosteroids are predominantly glucocorticoids with anti- inflammatory, immunosuppressive, anti-proliferative (anti-mitotic) and vasoconstrictive effects. Topical corticosteroids exert these effects on the skin to treat various inflammatory skin conditions (other than those arising from an infection), such as eczema, contact dermatitis, insect stings, psoriasis, lichen planus, discoid lupus erythematosus and alopecia areata. Topical corticosteroids are also available as compound preparations containing antibacterials, antifungals and salicylic acid for use in inflammatory skin conditions associated with bacterial and fungal infection according to the sensitivity of the infecting organism and hyperkeratosis respectively. They may also be used in conjunction with other topical agents eg coal tar or dithranol. Corticosteroids are not curative.1,2 Topical corticosteroids are available in four potencies: Mild, moderately potent, potent and very potent. The potency is determined by the amount of vasoconstriction produced as well as the formulation (ointments are more potent than creams), occlusion, the salt of the steroid, the presence of other ingredients and fluorination. The occlusion involves the covering of the treatment area is by a thin polythene film which enhances effectiveness as well as local and systemic toxicity. The salt of the steroid do influence the potency as dipropionate and butyrate salts are stronger than valerate salts. The presence of other ingredients such as salicylic acid or urea and fluorination increases potency (fluorinated corticosteroids e.g. Dermovate®, Haelan®, Metosyn® and Cutivate® have increased potency).1 There are no published systematic reviews comparing the effectiveness of different topical corticosteroids. Choice of agent is made according to patient need.3 The British Association of Dermatologists states that patients who fail to respond to one topical agent may respond to another and it is worthwhile rotating different types of topical agents.4 They also noted there is lack of evidence supporting twice-daily application of topical corticosteroids to be more effective than once daily application. The choice of topical corticosteroid depends on the condition being treated and its stage, the area of the body that is affected, and the age of the person. Mild forms of dermatitis may only require a mild corticosteroid whereas psoriasis may require a more potent steroid with the most potent treatments reserved for recalcitrant dermatoses. The least potent steroid that relieves the symptoms should be prescribed, and at an appropriate quantity. Patients should be advised to spread thinly over the affected area and use the fingertip unit as a measuring guide.2 Where long-term topical corticosteroids are required, gradual
2 withdrawal of the steroid may be needed to prevent rebound exacerbation of the condition. Use of emollient helps in reduction of use of steroids and where emollient is required, the corticosteroid should be applied 30 minutes after the emollient to ensure full absorption of the emollient. Areas where the skin is thin or flexural e.g. face, scrotum, groin, axillae and submammary area, usually require a weak or moderately-potent corticosteroid whereas areas where the skin is thick e.g. palms of the hands, soles of feet, scalp, or lichenified skin due to constant scratching, typically require more potent preparations.1 Pregnancy: Mildly potent, moderately potent and potent corticosteroids, if used correctly, are suitable for use during pregnancy. Some evidence suggested that very potent corticosteroids might be associated with low birth weight and will need specialist advice.1 Breastfeeding: Mildly potent, moderately potent and potent corticosteroids are considered suitable for use during breastfeeding. If applied to the breasts, the steroid should be washed off before breastfeeding to prevent the infant ingesting it.1 Cautions: Steroids are not recommended to be applied to the face for prolonged periods or for prolonged use in children. Potent and very potent corticosteroids are recommended to be used under specialist supervision. The use of potent or very potent corticosteroids in psoriasis can result in rebound relapse, development of pustular psoriasis, and local and systemic toxicity..1,2 Contraindications: Primary infections of the skin caused by bacteria, fungi or viruses, in acne, and rosacea. Potent corticosteroids are contraindicated in plaque psoriasis.1,2 Side-effects: Long-term continuous topical steroid therapy, especially with the potent and very potent preparations can produce atrophic skin changes such as thinning of the skin, irreversible striae and telangiectasia, and even adrenal suppression and Cushing’s syndrome. Contact dermatitis, irritation at site of application, spread and worsening of untreated infection, perioral dermatitis, acne/worsening of acne or rosacea, reversible depigmentation and hypertrichosis are other local side-effects reported.1,2 Tolerance may occur in response to continued use of any topical steroid and is related to duration of use rather than potency. The British Association of Dermatologists therefore recommends that No more than 100g of a moderately potent or higher potency preparation should be applied per month. Use of very potent preparations should be under dermatological supervision. Use of fingertip unit as a measure to help patients know how much ointment or cream to apply. No topical corticosteroid should be used regularly for more than four weeks without critical review. Potent corticosteroids should not be used regularly for more than 7 days. No unsupervised repeat prescriptions should be made. Patients should be reviewed every 3 months.4
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Table 1: Practical guidance to formulation choice of topical steroids based on the condition being treated, patient’s preference, its severity and location. 1,5
Selection of products available Formulation Formulation advantages Formulation disadvantages Body areas (not an exhaustive list)
A low viscosity, alcohol- or water- Very drying if alcohol is the base, and Scalp Betnovate® based liquids. Easy to apply and non- can sting sore skin. Betacap® greasy. ® Solutions Dermovate Scalp Application
A mixture of water suspended in oil, Contains preservatives in formulation, Face, limbs, trunks Cutivate® cream thicker than lotions- good which may cause irritation/allergic Flexures and genitals Elocon® cream moisturising qualities, absorb rapidly reactions. Lesser occlusive effect than Palms and soles Haelan® cream Cream into skin and cosmetically acceptable. ointments. Nerisone® cream Useful for exudating (weepy) and moist areas.
Less greasy and occlusive. Has a jelly- Lesser occlusive effect than creams and Face, Limbs, Trunk Synalar® gel like consistency, beneficial for ointments. Flexures and genitals Gel exudative inflammation and does not Palms and soles cause hair matting. Scalp and hairy areas
Less greasy and occlusive. Penetrate Contain alcohol, which has a drying Scalp and hairy Diprosone® lotion well on hairy areas and leave little effect. areas Locoid Crelo® lotion Lotions residue. Elocon® scalp lotion Betnovate® lotion
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Selection of products available Formulation Formulation advantages Formulation disadvantages Body areas (not an exhaustive list)
Paraffin-based, providing an occlusive Ointments are not suitable for hairy Face Betnovate® ointment emollient effect, which improved areas, flexures and genitals, as they Limbs Dermovate® ointment steroid absorption (this formulation may cause maceration and folliculitis. Trunk Haelan® ointment Ointment slightly increases potency). Most Greasy nature means they are not Palms and soles Modrasone® ointment useful for very dry skin and cosmetically acceptable. Paraffin-based hyperkeratotic areas. products are flammable.
Effectively delivers steroids to the Can only be used on the scalp. Scalp Bettamousse® foam Mousse (foam) scalp. Non-greasy. Clarelux® foam
Scalp Etrivex® shampoo Effectively delivers steroids to the Can only be used on the scalp. May be Shampoo scalp. Needs to be applied to a dry confusing for patients as this shampoo scalp and rinsed off 15 minutes. formulation is not used for washing hair.
Flexible and effective delivery method Not suitable for flexures, as occlusion Limbs Haelan® tape for targeted application under increases potency (Haelan® tape does Trunk occlusion. Helps protect easily not increase potency). May not stick to Palms and soles Tape damaged areas of skin (areas weepy areas. Courses limited to five constantly scratched), areas of very days for children. thick skin, and areas difficult to treat with other formulations (fingers).
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Hypersensitivity Reactions to Corticosteroids:6 Contact allergy is occasionally a complication of topical corticosteroid treatment and can be confirmed by appropriate patch testing. Patients generally present with a chronic dermatitis that is not exacerbated by, but fails to respond to corticosteroid therapy. In general, corticosteroid- sensitive patients react to several corticosteroids; this may be due to multiple sensitizations after the use of various different preparations, or due to a true cross-reactivity mechanism. In 1989, based on corticosteroid patch test results and their chemical structure, Coopman et al. concluded that cross reactions between corticosteroids occurred primarily within 4 groups: A: hydrocortisone type B: triamcinolone acetone type C: betamethasone type D: hydrocortisone-17-byturate type Group D was later subdivided into groups D1 and D2. The corticosteroids in each group have similar chemical structure, a fact which might explain the existence of a high cross-reactivity between the corticosteroids in each group (table 2). However, cases of cross reaction have also been reported between corticosteroids from group D2 and groups A and B, with Group D1 exhibiting quite low cross-reactivity with the other groups. Coopman’s classification has proved useful in the evaluation of reactions induced by topically administered corticosteroids, although it is not accepted by all. Table 2: Coopman classification of topical corticosteroids by the function of their allergenicity6
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In 1994, Wilkinson et al7 published a study that was contradicting Coopman et al’s classification table as they found many of their patients with multiple positive patch-test reactions to corticosteroids did not fit easily into the above four categories. Coopman and others have subsequently stated that not all of the cross-reactions that they see, fit into corticosteroid classes A to D. Wilkinson et al looked at the positive patch-test reactions to other corticosteroids in 96 patients who were allergic to hydrocortisone, to establish which substitutions were important in determining concomitant reactions. These patients were patch tested with tixocortol pivalate (1% petrolatum) as this compound is both a sensitive and specific marker for hypersensitivity to hydrocortisone. Patients positive on patch testing to tixocortol pivalate were then patch tested to a battery of corticosteroids, using Finn chambers® on Scanpor® tape, left on the skin of the back for 48 hours. The patch tests were read at 2 and 4 days and patients were asked to return for a further reading if they developed a reaction after 4 days. Reactions were scored as recommended by the International Contact Dermatitis Research Group, and were considered positive when a palpable erythematous (+) reaction or greater was present with the frequency of positive reactions to other corticosteroids being expressed as a percentage.
Results: It was found that the two commonest corticosteroid allergies occurring in patients hypersensitive to hydrocortisone were to hydrocortisone-17-butyrate and budesonide (Table 3). On the contrary, these three corticosteroids lie in different classes according to Coopman et al. (i.e. Class A: hydrocortisone, Class B: Budesonide, Class D: hydrocortisone-17-butyrate). The effect of the C6 and C9 substitution had greater statistical significance than that of the C16 and C17 substitutions as shown by the P-values after correction for other grouping (C6 and C9 P<0.0001; C16 and C17 P=0.005). The authors concluded that patients sensitised to topical hydrocortisone are most likely to concomitantly react to other non-C6 and –C9 substituted corticosteroids. They added that where facilities are not available to patch test to other corticosteroids (1% in ethanol), an alternative topical agent should be chosen based primarily on the C6 and C9 substitution, followed by the C16 and C17 substitution.
Table 3: Other positive patch test reactions in 96 patients allergic to hydrocortisone
Corticosteroid % positive n Hydrocortisone-17-butyrate 43.8 96 Budesonide 28.1 96 Methylprednisolone acetate 13.3 83 Alclometasone dipropionate 10.8 65 Flurandrenolone 7.23 83 Fluocortolone 3.61 83 Betamethasone valerate 5.21 96 Clobetasol butyrate 5.21 96 Clobetasol propionate 4.2 96
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Triamcinolone acetonide 3.6 83 Desoxymethasone 2.4 83 Beclomethasone 2.4 83 dipropionate Betamethasone 1.9 52 dipropionate Halcinonide 1.2 83 Fluocinonide 3.6 83 Diflucortolone valerate 1.2 83 Fluocinolone acetonide 1.2 83
Current formulary status::
The North Staffordshire Joint Formulary currently lists the following agents:
13.3 TOPICAL CORTICOSTEROIDS NICE TA81
Corticosteroid only preparations
Mild potency
Hydrocortisone (0.5%, 1%,
2.5%)
Moderate potency
Betamethasone valerate
0.025% (Betnovate-RD®)
Clobetasone butyrate
0.05% (Eumovate®)
Potent
Betamethasone valerate
0.1% (Betnovate®)
Hydrocortisone butyrate
0.1% (Locoid®)
Very potent
Clobetasol propionate
0.05% (Dermovate®)
Topical corticosteroids with antimicrobials
Mild potency
Canesten HC®
Daktacort®
Fucidin H®
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Vioform-Hydrocortisone®
Moderate potency
Trimovate®
Potent
Betnovate-C®
FuciBET®
Very potent
Dermovate-NN®
Scalp applications
Potent
Betamethasone valerate 0.1% scalp application
Diprosalic® (betamethasone 0.05%, salicylic acid 3%) scalp application
Very potent
Dermovate®
(clobetasol propionate 0.05%) scalp application
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RECOMMENDED CORTICOSTEROIDS
Recommended Pack Size and Drug Strength (w/w) Brand Formulation Primary Care Price* Mild Fluocinolone acetonide 0.0025% Synalar 1 in 10 dilution® Cream 50g (£4.58) Hydrocortisone 0.5% Generic Cream / Ointment 15g (£1.42 / £3.39) Hydrocortisone 1% Generic Cream / Ointment 15g (£1.12/£1.27) Mild with Antimicrobial Hydrocortisone / Clotrimazole 1% / 1% Canesten HC® Cream 30g (£2.42) Hydrocortisone / Miconazole 1% / 2% Daktacort® Cream / Ointment 30g (£2.48 / £2.50) Hydrocortisone acetate / Fusidic acid 1% / 2% Fucidin H® Cream 30g (£5.02) Moderate Fluocinolone acetonide 0.00625% Synalar 1 in 4 dilution® Cream / Ointment 50g (£4.84) 7.5 cm x 50cm (£9.27), Fludroxycortide 4 µg / cm2 Haelan® tape Polythene Adhesive Film 7.5 cm x 200 cm (£24.95) Betamethasone valerate 0.025% Betnovate-RD® Cream / Ointment 100g (£3.15) Clobetasone butyrate 0.05% Eumovate® Cream / Ointment 30g (£1.86), 100g (£5.44) Moderate with Antimicrobial Clobetasone butyrate / Oxytetracycline 0.05% / 3% / Trimovate® Cream 30g (£3.29)** / Nystatin 100,000 units/g Potent Fluocinolone acetonide 0.025% Synalar® Cream / Ointment 30g (£4.14), 100g (£11.75) Hydrocortisone butyrate 0.1% Locoid® Cream / Ointment 30g (£1.60), 100g (£4.93) Betamethasone valerate 0.1% Betnovate® Cream 30g (£2.73), 100g (£9.10) Betamethasone valerate 0.1% Betnovate® ointment 30g (£3.16), 100g (£10.53)
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Drug Strength (w/w) Brand Formulation Recommended Pack Size and Primary Care Price* Potent With Antimicrobial Betamethasone valerate / Clioquinol 0.1% / 3% Generic Cream / Ointment 30g (£9.48) Betamethasone valerate / Fusidic Acid 0.1% / 2% Fucibet® Cream 30g (£5.32), 60g (£10.63) Fluocinolone acetonide / Clioquinol 0.025% / 3% Synalar C® Cream / Ointment 15g (£2.66)** Fluocinolone acetonide / Neomycin 0.025% / 0.5% Synalar N® Cream / Ointment 30g (£4.36)** Potent With Salicylic Acid Betamethasone dipropionate / Salicylic 0.05% / 3% Diprosalic® Ointment 30g (£3.18), 100g (£9.14) Acid Potent Scalp Application Betamethasone valerate 0.1% Betacap® Scalp Application 100ml (£3.75) Betamethasone dipropionate / Salicylic 0.05% / 2% Diprosalic® Scalp Application 100ml (£10.10) acid Fluocinolone acetonide 0.025% Synalar® Gel 30g (£5.56), 60g (£10.02) Very Potent Clobetasol propionate 0.05% Dermovate® Cream / Ointment 30g (£2.69), 100g (£7.90) Diflucortolone valerate 0.3% Nerisone Forte® Oily Cream /Ointment 15g (£2.09) Very Potent Scalp Application Clobetasol propionate 0.05% Dermovate® Scalp Application 30ml (£3.07), 100ml (£10.42) Very Potent with Antimicrobial Clobetasol propionate / Neomycin 0.05% / 0.5% / 100,000 Generic Cream / Ointment 30g (£64.00)*** sulphate / Nystatin units/g
*Primary care costs were obtained Drug Tariff December 2013.8 **Costs unavailable in the Drug Tariff. Costs obtained from the C&D.9 ***Prices have been taken from the British National Formulary (BNF) 66 September 2013.10
Table updated by Monjur Ali (Clinical Pharmacist) – February 2014.
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Cost analysis:
Expenditure in Primary and Secondary Care for a 12-month period (June 2012 - May 2013):
Product UHNS STOKE CCG NORTH STAFF CCG
Haelan® Tape £142.49 £2,575.16 £2,131.05
Trimovate® cream £1,335.67 £14,387.83 £11,532.92
Diprosalic® ointment £197.10 £7,939.59 £5,197.16
Nerisone Forte® oily cream £2.20 £3.90 £9.67
Nerisone Forte® ointment £0.00 £3.89 £3.87
Fluocinolone acetonide 0.0025% £17.87 £343.50 £415.14 (Synalar 1 in 10 dilution®) cream Hydrocortisone 0.5% cream £100.85 £4,728.99 £2,931.30 Hydrocortisone 0.5% ointment £48.30 £2,183.44 £1,041.39 Hydrocortisone 1% cream £332.19 £18,602.12 £14,969.59 Hydrocortisone 1% ointment £75.38 £5,799.51 £3,632.77 Hydrocortisone 2.5% cream £0.00 £5,020.17 £4,301.19 Hydrocortisone 2.5% ointment £0.00 £3,638.92 £2,173.13
Canesten HC® cream £155.36 £3,060.76 £2,524.74
Daktacort® cream £380.77 £7,255.88 £4,739.01 Daktacort® ointment £40.60 £1,501.36 £635.57 Fucidin H® cream £726.12 £12,689.87 £7,449.48 Synalar 1 in 4 dilution® (fluocinolone £4.63 £527.90 £1,047.72 acetonide 0.00625%) cream / ointment Betnovate-RD® (betamethasone valerate £410.03 £14,184.51 £8,737.66 0.025%) cream / ointment Eumovate® (clobetasone butyrate) cream / £1,112.05 £5,471.59 £5,877.75 ointment Fluocinolone Acetonide (Synalar®) 0.025% £75.40 £2,663.10 £1,287.01 cream/ointment Synalar® Gel (fluocinolone acetonide 0.025%) £152.65 £2,391.21 £1,102.45
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Product UHNS STOKE CCG NORTH STAFF CCG Hydrocortisone butyrate (Locoid®) 0.1% £12.59 £462.99 £384.44 cream /ointment Betamethasone valerate (Betnovate®) 0.1% £555.78 £22,159.58 £18,830.25 cream Betnovate® 0.1% ointment £615.26 £12,145.12 £7,708.04 Betacap® (betamethasone valerate 0.1%) £146.58 £563.15 £267.46 scalp application Betnovate® (betamethasone valerate 0.1%) £33.30 £10,226.11 £8,721.89 scalp application Diprosalic® scalp application (betamethasone £214.02 £4,562.93 £3,135.35 dipropionate 0.05% + salicylic acid 2%) Betamethasone valerate 0.1% + Clioquinol £1503.76 £1,529.98 £889.60 3% cream/ointment Fucibet® cream £959.03 £20,128.90 £12,569.69
Synalar C® (fluocinolone acetonide 0.025% + £3.04 £327.36 £231.49 clioquinol 3%) cream/ointment Synalar N® (fluocinolone acetonide 0.025% + £4.93 £197.72 £181.45 neomycin 0.5%) cream/ointment Clobetasol propionate 0.05% (Dermovate®) £2,079.24 £11,093.65 £7,416.87 cream / ointment Clarelux® Foam (=scalp application) £527.56 £347.49 £10.23 (clobetasol propionate 0.05%) (inc Dermovate® and Etrivex® brands) Clobetasol propionate 0.05% + neomycin £3,033.57 £8,851.84 £4,370.14 sulfate 0.5% + nystatin 100,000 units/g cream Clobetasol propionate 0.05% + neomycin sulfate 0.5% + nystatin 100,000 units/g £0.00 £650.00 £177.18 ointment
Expenditure for UHNS reflects items dispensed via UHNS dispensary (i.e. inpatients,) Lloyds pharmacy &FPHP10 prescriptions
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References
1 NICE CKS. Corticosteroids-topical (skin), nose and eyes. Available at: http://cks.nice.org.uk/corticosteroids-topical-skin-nose-and-eyes.
contact dermatitis from hydrocortisone. British Journal of Dermatology 1995;132:766-771. 8 NHS Electronic Drug Tariff, February 2014. Available from http://www.ppa.org.uk/ppa/edt_intro.htm
Produced by Susheela Sumelingam Rotational Specialist Pharmacist University Hospital of North Staffordshire Telephone: 01782 674542 e-mail: [email protected]
Produced for use within the NHS. Not to be reproduced for commercial purposes.
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