Betamethasone valerate is a potent topical corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of steroid responsive dermatoses. Clioquinol is an antibacterial antifungal drug.

Topical preparations combining betamethasone valerate and clioquinol are indicated for the treatment of the following conditions where secondary bacterial and/or fungal infection is present, suspected or likely to occur:

-       Atopic dermatitis

-       Nummular dermatitis (discoid eczema)

-       Prurigo nodularis

-       Psoriasis (excluding widespread plaque psoriasis)

-       Lichen simplex chronicus (neurodermatitis) and lichen planus

-       Seborrhoeic dermatitis

-       Irritant or allergic contact dermatitis

-       Insect bite reactions

-       Miliaria (prickly heat)

-       Anal and genital intertrigo

-       Otitis externa.

Ointments are especially appropriate for dry, lichenified or scaly lesions.

Adults and adolescents 

Apply thinly and gently rub in using only enough to cover the entire affected area once or twice daily for up to four weeks until improvement occurs, then reduce the frequency of application or change the treatment to a less potent preparation. Allow adequate time for absorption after each application before applying an emollient.

In the more resistant lesions, such as the thickened plaques of psoriasis on elbows and knees, the effect of BETNOVATE-C can be enhanced, if necessary, by occluding the treatment area with polythene film.  Overnight occlusion only is usually adequate to bring about a satisfactory response in such lesions, thereafter improvement can usually be maintained by regular application without occlusion.

If the condition worsens or does not improve within two to four weeks, treatment and diagnosis should be re-evaluated.

Atopic dermatitis (eczema)

Therapy with BETNOVATE-C should be gradually discontinued once control is achieved and an emollient continued as maintenance therapy.

Rebound of pre-existing dermatoses can occur with abrupt discontinuation of BETNOVATE-C.

Recalcitrant dermatoses

Patients who frequently relapse

Once an acute episode has been treated effectively with a continuous course of topical corticosteroid, intermittent dosing (once daily, twice weekly, without occlusion) may be considered. This has been shown to be helpful in reducing the frequency of relapse.

Application should be continued to all previously affected sites or to known sites of potential relapse. This regime should be combined with routine daily use of emollients.  The condition and the benefits and risks of continued treatment must be re-evaluated on a regular basis.

Children aged 1 year and over

BETNOVATE-C is suitable for use in children and infants (1 year and over) at the same dose as adults. A possibility of increased absorption exists in very young children, thus betamethasone valerate-clioquinol is contraindicated in neonates and infants under 1 year of age (see Contraindications).

Children are more likely to develop local and systemic side effects of topical corticosteroids and, in general, require shorter courses and less potent agents than adults.

Care should be taken when using BETNOVATE-C to ensure the amount applied is the minimum that provides therapeutic benefit.

Elderly

BETNOVATE-C is suitable for use in the elderly. Clinical studies have not identified differences in responses between the elderly and younger patients. The greater frequency of decreased hepatic or renal function in the elderly may delay elimination if systemic absorption occurs. Therefore the minimum quantity should be used for the shortest duration to achieve the desired clinical benefit.

Renal/Hepatic Impairment

In case of systemic absorption (when application is over a large surface area for a prolonged period), metabolism and elimination may be delayed therefore increasing the risk of systemic toxicity. Therefore the minimum quantity should be used for the shortest duration to achieve the desired clinical benefit.

BETNOVATE-C is contraindicated in children under 1 year of age. The following conditions should not be treated with BETNOVATE-C: - Rosacea - Acne vulgaris - Perioral dermatitis - Pruritus without inflammation - Perianal or genital pruritus - Primary cutaneous viral infections - Primary infected skin lesions caused by infection with fungi or bacteria - Primary or secondary infections due to yeast

Hypersensitivity

BETNOVATE-C should be used with caution in patients with a history of hypersensitivity to betamethasone, clioquinol or to any of the excipients in the preparation, or to iodine. Local hypersensitivity reactions (see Adverse Reactions) may resemble symptoms of the condition under treatment.

Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression

Manifestations of hypercortisolism (Cushing’s syndrome) and reversible hypothalamic-pituitary-adrenal (HPA) axis suppression can occur in some individuals as a result of increased systemic absorption of topical corticosteroids. If either of the above are observed, withdraw the drug gradually by reducing the frequency of application, or by substituting a less potent corticosteroid. Abrupt withdrawal of treatment may result in glucocorticosteroid insufficiency (see Adverse Reactions).

Risk factors for increased corticosteroidal systemic effects are:

·       Potency and formulation of topical corticosteroid

·       Duration of exposure

·       Application to a large surface area

·       Use on occluded areas of skin (e.g. on intertriginous areas or under occlusive dressings (nappies may act as an occlusive dressing)

·       Increasing hydration of the stratum corneum

·       Use on thin skin areas such as the face

·       Use on broken skin or other conditions where the skin barrier may be impaired.

Visual Disturbances

Visual disturbance has been reported by patients using systemic and /or topical corticosteroids. If a patient has blurred vision or other visual disturbances, consider evaluation of possible causes which may include cataract, glaucoma or central serous chorioretinopathy.

Use in children

In comparison with adults, children and infants may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic adverse effects. This is because children have an immature skin barrier and a greater surface area to body weight ratio compared with adults.

In children under 12 years, long-term continuous topical corticosteroid therapy should be avoided where possible, as adrenal suppression can occur.

Use in psoriasis

Topical corticosteroids should be used with caution in psoriasis as rebound relapses, development of tolerance, risk of generalised pustular psoriasis and development of local or systemic toxicity due to impaired barrier function of the skin have been reported in some cases (see Adverse Reactions).  If used in psoriasis careful patient supervision is important.

Dilution

Products which contain antimicrobial agents should not be diluted.

Neurotoxicity

There is a theoretical risk of neurotoxicity from the topical application of clioquinol, particularly when BETNOVATE-C is used for prolonged periods or under occlusion.

Application to the face

Prolonged application to the face is undesirable as this area is more susceptible to atrophic changes.

Application to the eyelids

If applied to the eyelids, care is needed to ensure that the preparation does not enter the eye, as cataract and glaucoma might result from repeated exposure.

Infection

Extension of infection may occur due to the masking effect of the steroid.  Any spread of infection requires withdrawal of topical corticosteroid therapy and administration of appropriate systemic antimicrobial therapy.

Infection risk with occlusion

Bacterial infection is encouraged by the warm, moist conditions within skinfolds or caused by occlusive dressings. When using occlusive dressings, the skin should be cleansed before a fresh dressing is applied.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat the dermatitis around chronic leg ulcers. However, this use may be associated with a higher occurrence of local hypersensitivity reactions and an increased risk of local infection.

Flammability risk

Product contains paraffin. Instruct patients not to smoke or go near naked flames due to the risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.

Staining

BETNOVATE-C may stain hair, skin or fabric, and the application should be covered with a dressing to protect clothing

Co-administered drugs that can inhibit CYP3A4 (e.g. ritonavir, itraconazole) have been shown to inhibit the metabolism of corticosteroids leading to increased systemic exposure. The extent to which this interaction is clinically relevant depends on the dose and route of administration of the corticosteroids and the potency of the CYP3A4 inhibitor.

Theoretical concerns exist that oculotoxic effects of vigabatrin may be additive with clioquinol. Vigabatrin should not be used with clioquinol.

Fertility

There are no data in humans to evaluate the effect of BETNOVATE-C on fertility.

Pregnancy

There are limited data from the use of BETNOVATE-C in pregnant women.

Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development (see Pre-clinical safety data).  The relevance of this finding to human beings has not been established. However, administration of BETNOVATE-C during pregnancy should only be considered if the expected benefit to the mother outweighs the risk to the foetus. The minimum quantity should be used for the minimum duration.

Lactation

The safe use of BETNOVATE-C during lactation has not been established.

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk.

Administration of BETNOVATE-C during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant.

If used during lactation, BETNOVATE-C should not be applied to the breasts to avoid accidental ingestion by the infant.

There have been no studies to investigate the effect of BETNOVATE-C on driving performance or the ability to operate machinery. A detrimental effect on such activities would not be anticipated from the adverse reaction profile of BETNOVATE-C.

Clinical Trial and Post-marketing Data 

Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and by frequency.  Frequencies are defined as: very common (³1/10), common (³1/100 and <1/10), uncommon (³1/1000 and <1/100), rare (³1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports. 

Infections and Infestations 

Very rare                     Opportunistic infection

Immune System Disorders 

Very rare                     Local hypersensitivity

Endocrine Disorders 

Very rare                     Hypothalamic-pituitary adrenal (HPA) axis suppression: (see also Skin and Subcutaneous Tissue Disorders) Cushingoid features (e.g. moon face, central obesity), delayed weight gain/growth retardation in children, osteoporosis, glaucoma, hyperglycaemia/glucosuria, cataract, hypertension, increased weight/obesity, decreased endogenous cortisol levels

Skin and Subcutaneous Tissue Disorders 

Common                     Pruritus, local skin burning/pain of skin

Very rare                     Allergic contact dermatitis/dermatitis, erythema, rash, urticaria, pustular psoriasis (see Warnings and Precautions), skin thinning*/skin atrophy*, skin wrinkling*, skin dryness*, striae*, telangiectasias*, pigmentation changes*, hypertrichosis, exacerbation of underlying symptoms, alopecia*, trichorrhexis*, hair discoloration

General Disorders and Administration Site Conditions

Very rare                                 Application site irritation/pain

 

*Skin features of hypothalamic-pituitary adrenal (HPA) axis suppression

 

To report any side effect(s):

Kingdom of Saudi Arabia

-National Pharmacovigilance centre (NPC)

• Fax: +966-11-205-7662
• SFDA Call Center: 19999
• E-mail: 19TUnpc.drug@sfda.gov.saU19T

·      Website: 19Thttps://ade.sfda.gov.sa19T

-GlaxoSmithKline - Head Office, Jeddah

• Tel:  +966-12-6536666
• Mobile: +966-56-904-9882
• Email: 19Tsaudi.safety@gsk.com19T   
• Website: 19Thttps://gskpro.com/en-sa/19T
• P.O Box 55850, Jeddah 21544, Saudi Arabia.

 

For any information about this medicinal product, please contact:

GlaxoSmithKline - Head Office, Jeddah

• Tel:  +966-12-6536666
• Mobile: +966-56-904-9882
• Email: 19Tgcc.medinfo@gsk.com19T
• Website: 19Thttps://gskpro.com/en-sa/19T
• P.O. Box 55850, Jeddah 21544, Saudi Arabia

Symptoms and Signs

Topicall applied BETNOVATE-C may be absorbed in sufficient amounts to produce systemic effects. Acute overdosage is very unlikely to occur, however, in the case of chronic overdosage or misuse the features of hypercortisolism may appear (see Adverse Reactions).

Treatment

In the event of chronic overdose or misuse, topical corticosteroids should be withdrawn gradually by reducing the frequency of application, or by substituting a less potent corticosteroid because of the risk of adrenal insufficiency.

Further management should be as clinically indicated or as recommended by the National Poisons Centre, where available.

 ATC code

D07BC01 Betamethasone and antiseptics.

Mechanism of action

Betamethasone valerate

Topical corticosteroids act as anti-inflammatory agents via multiple mechanisms to inhibit late phase allergic reactions, including decreasing the density of mast cells, decreasing chemotaxis and activation of eosinophils, decreasing cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibiting the metabolism of arachidonic acid.

Clioquinol

The mechanism of action of clioquinol is not known but its action is probably due to its iodine content.

Pharmacodynamic effects

Betamethasone valerate

Topical corticosteroids have anti-inflammatory, antipruritic and vasoconstrictive properties.

Clioquinol

Clioquinol has antibacterial and antifungal action against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Candida albicans. It has weak activity against Staphylococcus pyogenes and no activity against Pseudomonas.

Absorption

Betamethasone valerate

Topical corticosteroids can be systematically absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.

The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection.

Metabolism

Betamethasone valerate

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver.

Elimination

Betamethasone valerate

Topical corticosteroids are excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

Clioquinol

Clioquinol is excreted in the urine as glucuronide and sulphate metabolites.

Special Patient Populations

No Text.

Clinical Studies

No Text.

Non-clinical studies have not been conducted with BETNOVATE-C.

Betamethasone valerate and clioquinol individually have been evaluated in animal toxicity tests, and the following statements reflect the information available on the individual components.

Carcinogenesis

No text.

Genotoxicity

Betamethasone valerate

No text.

Clioquinol

Clioquinol was not mutagenic in vitro.

Reproductive Toxicology

Fertility

No text.

Pregnancy

Betamethasone valerate

Subcutaneous administration of betamethasone 17-valerate to mice or rats at doses ³0.1 mg/kg/day or rabbits at doses ³12 micrograms/kg/day during pregnancy produced foetal abnormalities including cleft palate and intrauterine growth retardation.

Clioquinol

Oral administration of clioquinol to rats during pregnancy was associated with reduced foetal body weight at doses ³120 mg/kg/day and delays in ossification at doses ³300 mg/kg/day.

Liquid paraffin

White soft paraffin

For important information about some of these excipients see Warnings and Precautions.

No incompatibilities have been identified.

The expiry date is indicated on the packaging.

Store below 30°C.

BETNVATE-C ointment is packed in collapsible aluminium tubes unlacquered or internally coated with an epoxy resin based lacquer and closed with a cap.

Do not dilute.

 

 

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