SUMMARY OF PRODUCT CHARACTERISTICS

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS Prduct Summary 1. Trade Name f the Medicinal Prduct Betnvate Cream 2. Qualitative and Quantitative Cmpsitin Betamethasne Valerate 0.122% W / W Excipients with knwn effect: Chlrcresl Cetstearyl alchl Fr the full list f excipients, see sectin Pharmaceutical Frm Aqueus Cream Clinical Particulars 4.1 Therapeutic indicatins Betamethasne valerate is a ptent tpical crticsterid indicated fr adults, elderly and children ver 1 year fr the relief f the inflammatry and pruritic manifestatins f sterid respnsive dermatses. These include the fllwing: Atpic dermatitis (including infantile atpic dermatitis) Nummular dermatitis (discid eczema) Prurig ndularis Psriasis (excluding widespread plaque psriasis) Lichen simplex chrnicus (neurdermatitis) and lichen planus Sebrrheic dermatitis Irritant r allergic cntact dermatitis Discid lupus erythematsus Adjunct t systemic sterid therapy in generalised erythrderma Insect bite reactins 4.2 Pslgy and methd f administratin Rute f administratin: Cutaneus Creams are especially apprpriate fr mist r weeping surfaces. Apply thinly and gently rub in using nly enugh t cver the entire affected area nce r twice daily fr up t 4 weeks until imprvement ccurs, then reduce the frequency f applicatin r change the treatment t a less ptent preparatin.

2 Allw adequate time fr absrptin after each applicatin befre applying an emllient. In the mre resistant lesins, such as the thickened plaques f psriasis n elbws and knees, the effect f betamethasne valerate can be enhanced, if necessary, by ccluding the treatment area with plythene film. Overnight cclusin nly is usually adequate t bring abut a satisfactry respnse in such lesins; thereafter, imprvement can usually be maintained by regular applicatin withut cclusin. If the cnditin wrsens r des nt imprve within 2-4 weeks, treatment and diagnsis shuld be re-evaluated. Therapy with betamethasne valerate shuld be gradually discntinued nce cntrl is achieved and an emllient cntinued as maintenance therapy. Rebund f pre-existing dermatses can ccur with abrupt discntinuatin f betamethasne valerate. Recalcitrant dermatses Patients wh frequently relapse Once an acute episde has been treated effectively with a cntinuus curse f tpical crticsterid, intermittent dsing (apply nce a day twice a week withut cclusin) may be cnsidered. This has been shwn t be helpful in reducing the frequency f relapse. Applicatin shuld be cntinued t all previusly affected sites r t knwn sites f ptential relapse. This regimen shuld be cmbined with rutine daily use f emllients. The cnditin and the benefits and risks f cntinued treatment must be re-evaluated n a regular basis. Paediatric ppulatin Betamethasne valerate is cntraindicated in children under ne year f age. Children are mre likely t develp lcal and systemic side effects f tpical crticsterids and, in general, require shrter curses and less ptent agents than adults; therefre, curses shuld be limited t five days and cclusin shuld nt be used. Care shuld be taken when using betamethasne valerate t ensure the amunt applied is the minimum that prvides therapeutic benefit. Elderly Clinical studies have nt identified differences in respnses between the elderly and yunger patients. The greater frequency f decreased hepatic r renal functin in the elderly may delay eliminatin if systemic absrptin ccurs. Therefre the minimum quantity shuld be used fr the shrtest duratin t achieve the desired clinical benefit. Renal / Hepatic Impairment In case f systemic absrptin (when applicatin is ver a large surface area fr a prlnged perid) metablism and eliminatin may be delayed therefre increasing the risk f systemic txicity. Therefre the minimum quantity shuld be used fr the shrtest duratin t achieve the desired clinical benefit. 4.3 Cntra-indicatins

3 Hypersensitivity t the active substance r any f the excipients in the excipients listed in sectin 6.1. The fllwing cnditins shuld nt be treated with betamethasne valerate: Untreated cutaneus infectins Rsacea Acne vulgaris Pruritus withut inflammatin Perianal and genital pruritus Periral dermatitis Betamethasne valerate is cntraindicated in dermatses in infants under ne year f age, including dermatitis 4.4 Special warnings and precautins fr use Betamethasne valerate shuld be used with cautin in patients with a histry f lcal hypersensitivity t ther crticsterids. Lcal hypersensitivity reactins (see sectin 4.8) may resemble symptms f the cnditin under treatment. Manifestatins f hypercrtislism (Cushing s syndrme) and reversible hypthalamicpituitary-adrenal (HPA) axis suppressin, leading t gluccrticsterid insufficiency, can ccur in sme individuals as a result f increased systemic absrptin f tpical sterids. If either f the abve are bserved, withdraw the drug gradually by reducing the frequency f applicatin, r by substituting a less ptent crticsterid. Abrupt withdrawal f treatment may result in gluccrticsterid insufficiency (see sectin 4.8). Risk factrs fr increased systemic effects are: Ptency and frmulatin f tpical sterid Duratin f expsure Applicatin t a large surface area Use n ccluded areas f skin e.g. n intertriginus areas r under cclusive dressings (in infants the nappy may act as an cclusive dressing) Increasing hydratin f the stratum crneum Use n thin skin areas such as the face Use n brken skin r ther cnditins where the skin barrier may be impaired In cmparisn with adults, children may absrb prprtinally larger amunts f tpical crticsterids and thus be mre susceptible t systemic adverse effects. This is because children have an immature skin barrier and a greater surface area t bdy weight rati cmpared with adults.

4 Paediatric ppulatin In infants and children under 12 years f age, treatment curses shuld be limited t five days and cclusin shuld nt be used; lng-term cntinuus tpical crticsterid therapy shuld be avided where pssible, as adrenal suppressin can ccur. Infectin risk with cclusin Bacterial infectin is encuraged by the warm, mist cnditins within skin flds r caused by cclusive dressings. When using cclusive dressings, the skin shuld be cleansed befre a fresh dressing is applied. Use in Psriasis Tpical crticsterids shuld be used with cautin in psriasis as rebund relapses, develpment f tlerances, risk f generalised pustular psriasis and develpment f lcal r systemic txicity due t impaired barrier functin f the skin have been reprted in sme cases. If used in psriasis careful patient supervisin is imprtant. Applicatin t the face Prlnged applicatin t the face is undesirable as this area is mre susceptible t atrphic changes; therefre, treatment curses shuld be limited t five days and cclusin shuld nt be used. Applicatin t the eyelids If applied t the eyelids, care is needed t ensure that the preparatin des nt enter the eye, as cataract and glaucma might result frm repeated expsure. Visual disturbance Visual disturbance may be reprted with systemic and tpical crticsterid use. If a patient presents with symptms such as blurred visin r ther visual disturbances, the patient shuld be cnsidered fr referral t an phthalmlgist fr evaluatin f pssible causes which may include cataract, glaucma r rare diseases such as central serus chriretinpathy (CSCR) which have been reprted after use f systemic and tpical crticsterids Cncmitant infectin Apprpriate antimicrbial therapy shuld be used whenever treating inflammatry lesins which have becme infected. Any spread f infectin requires withdrawal f tpical crticsterid therapy and administratin f apprpriate antimicrbial therapy. Chrnic leg ulcers Tpical crticsterids are smetimes used t treat the dermatitis arund chrnic leg ulcers. Hwever, this use may be assciated with a higher ccurrence f lcal hypersensitivity reactins and an increased risk f lcal infectin. Healthcare prfessinals shuld be aware that if this prduct cmes int cntact with dressings, clthing and bedding, the fabric can be easily ignited with a naked flame. Patients shuld be warned f this risk and advised t keep away frm fire when using this prduct. Betnvate cntains chlrcresl which may cause allergic reactins and cetstearyl alchl which may cause lcal skin reactins (e.g. cntact dermatitis). 4.5 Interactin with ther medicaments and ther frms f interactin

5 C-administered drugs that can inhibit CYP3A4 (e.g. ritnavir, itracnazle) have been shwn t inhibit the metablism f crticsterids leading t increased systemic expsure. The extent t which this interactin is clinically relevant depends n the dse and rute f administratin f the crticsterids and the ptency f the CYP3A4 inhibitr Fertility, pregnancy and lactatin Fertility There are n data in humans t evaluate the effect f tpical crticsterids n fertility. Pregnancy There are limited data frm the use f betamethasne valerate in pregnant wmen. Tpical administratin f crticsterids t pregnant animals can cause abnrmalities f fetal develpment. (see sectin 5.3). The relevance f this finding t humans has nt been established; hwever, administratin f betamethasne valerate during pregnancy shuld nly be cnsidered if the expected benefit t the mther utweighs the risk t the fetus. The minimum quantity shuld be used fr the minimum duratin. Lactatin The safe use f tpical crticsterids during lactatin has nt been established. It is nt knwn whether tpical administratin f crticsterids culd result in sufficient systemic absrptin t prduce detectable amunts in breast milk. Administratin f betamethasne valerate during lactatin shuld nly be cnsidered if the expected benefit t the mther utweighs the risk t the infant. If used during lactatin betamethasne valerate shuld nt be applied t the breasts t avid accidental ingestin by the infant. 4.7 Effect n ability t drive and use machines There have been n studies t investigate the effect f betamethasne valerate n driving perfrmance r the ability t perate machinery. A detrimental effect n such activities wuld nt be anticipated frm the adverse reactin prfile f tpical betamethasne valerate. 4.8 Undesirable effects Adverse drug reactins (ADRs) are listed belw by MedDRA system rgan class and by frequency. Frequencies are defined as: very cmmn ( 1/10), cmmn ( 1/100 and <1/10), uncmmn ( 1/1,000 and <1/100), rare ( 1/10,000 and <1/1,000) and very rare (<1/10,000), including islated reprts. Pst-marketing data Infectins and Infestatins Opprtunistic infectin Immune System Disrders Hypersensitivity, generalised rash Endcrine Disrders Hypthalamic-pituitary adrenal (HPA) axis suppressin

6 Cushingid features (e.g. mn face, central besity), delayed weight gain/grwth retardatin in children, steprsis, glaucma, hyperglycaemia/glucsuria, cataract, hypertensin, increased weight/besity, decreased endgenus crtisl levels, alpecia, trichrrhexis Skin and Subcutaneus Tissue Disrders Cmmn Pruritus, lcal skin burning /skin pain Allergic cntact dermatitis /dermatitis, erythema, rash, urticaria, pustular psriasis, skin thinning* / skin atrphy*, skin wrinkling*, skin dryness*, striae*, telangiectasias*, pigmentatin changes*,hypertrichsis, exacerbatin f underlying symptms General Disrders and Administratin Site Cnditins Applicatin site irritatin/pain *Skin features secndary t lcal and/r systemic effects f hypthalamic-pituitary adrenal (HPA) axis suppressin. Eye disrders Nt knwn Visin, blurred (see als sectin 4.4) Reprting f suspected reactins: Reprting suspected adverse reactins after authrisatin f the medicinal prduct is imprtant. It allws cntinued mnitring f the benefit/risk balance f the medicinal prduct. Healthcare prfessinals are asked t reprt any suspected adverse reactins via the natinal system belw: ADR Reprting Website: Overdse Symptms and signs Tpically applied betamethasne valerate may be absrbed in sufficient amunts t prduce systemic effects. Acute verdsage is very unlikely t ccur, hwever, in the case f chrnic verdsage r misuse the features f hypercrtislism may ccur (see sectin 4.8). Treatment In the event f verdse, betamethasne valerate shuld be withdrawn gradually by reducing the frequency f applicatin, r by substituting a less ptent crticsterid because f the risk f gluccrticsterid insufficiency. Further management shuld be as clinically indicated r as recmmended by the natinal pisns centre, where available.

7 Pharmaclgical Prperties 5.1 Pharmacdynamic prperties ATC cde D07AC Crticsterids, ptent (grup III) Mechanism f actin Tpical crticsterids act as anti-inflammatry agents via multiple mechanisms t inhibit late phase allergic reactins including decreasing the density f mast cells, decreasing chemtaxis and activatin f esinphils, decreasing cytkine prductin by lymphcytes, mncytes, mast cells and esinphils, and inhibiting the metablism f arachidnic acid. Pharmacdynamic effects Tpical crticsterids have anti-inflammatry, antipruritic, and vascnstrictive prperties. 5.2 Pharmackinetic prperties Absrptin Tpical crticsterids can be systemically absrbed frm intact healthy skin. The extent f percutaneus absrptin f tpical crticsterids is determined by many factrs, including the vehicle and the integrity f the epidermal barrier. Occlusin, inflammatin and/r ther disease prcesses in the skin may als increase percutaneus absrptin. Distributin The use f pharmacdynamic endpints fr assessing the systemic expsure f tpical crticsterids is necessary because circulating levels are well belw the level f detectin. Metablism Once absrbed thrugh the skin, tpical crticsterids are handled thrugh pharmackinetic pathways similar t systemically administered crticsterids. They are metablised, primarily in the liver. Eliminatin Tpical crticsterids are excreted by the kidneys. In additin, sme crticsterids and their metablites are als excreted in the bile. 5.3 Preclinical safety data Reprductive txicity Subcutaneus administratin f betamethasne valerate t mice r rats at dses 0.1 mg/kg/day r rabbits at dses 12 micrgrams/kg/day during pregnancy prduced fetal abnrmalities including cleft palate and intrauterine grwth retardatin. The effect n fertility f betamethasne valerate has nt been evaluated in animals.

8 Pharmaceutical Particulars 6.1 List f excipients Chlrcresl Cetmacrgl 1000 Cetstearyl Alchl White Sft Paraffin Liquid Paraffin Sdium Acid Phsphate Phsphric Acid Sdium Hydrxide Purified Water 6.2 Incmpatibilities Nne knwn. 6.3 Shelf life Tubes 500gm pts 36 Mnths 18 mnths 6.4 Special precautins fr strage Stre belw 25 C. 6.5 Nature and cntents f cntainer 15gm, 30gm and 100gm cllapsible aluminium tubes internally cated with an epxy resin based lacquer and clsed with a cap. 500mg paque high density plythene pts with black urea frmaldehyde screw caps having a steran faced wad. Nt all pack sizes may be marketed 6.6 Special precautins fr dispsal N special requirements. 7. Marketing Authrisatin Hlder Glax Wellcme UK Ltd., T/A GlaxSmithKline UK Stckley Park West, Uxbridge, Middlesex UB11 1BT

9 8. Marketing Authrisatin Number MA167/ Date f First Authrisatin/Renewal f Authrisatin 12 th September 2005 / 21 st February Date f (Partial) Revisin f Text 31 st Octber 2017