SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Xepin 5% w/w Cream

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Doxepin hydrochloride 5% w/w

3.    PHARMACEUTICAL FORM

Cream for topical application to the skin.

4    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

For the relief of pruritus associated with eczema.

4.2 Posology and method of administration

Adults and children over 12 years

A thin film of Xepin should be applied three to four times daily, to the affected area only. Clinical experience has shown that drowsiness is significantly more common in patients applying cream to more than 10% of the body surface area, therefore, the maximum coverage should be less than 10% of body surface area. For an average sized patient, this would equate to 3g of Xepin per application and not more than 12g of Xepin per day. If excessive drowsiness does occur, it may be necessary to reduce the number of applications, the amount of cream applied and/or the percentage of body surface area treated.

Occlusive dressings or clothing may increase the absorption of any topically applied drug, including Xepin; therefore, caution must be exercised when utilising occlusive dressings.

Children under 12 years

There are insufficient data to enable dosage recommendations to be made for children.

Elderly

There are no specific dosage recommendations for elderly patients.

4.3. Contra-indications

Xepin is contra-indicated in individuals who have shown pervious hypersensitivity to any of its components.

4.4 Special warnings and precautions for use

Drowsiness may occur with the use of Xepin. Clinical trial data demonstrate that drowsiness is observed principally in patients receiving treatment to greater than 10% of body surface area and that drowsiness is transient, usually remitting after the first few days of treatment.

Patients should, therefore be warned of this possibility and cautioned against driving or operating machinery if they become drowsy while being treated with Xepin.

Patients should also be warned that the effects of alcohol could be potentiated. In view of the known adverse effects of orally administered doxepin hydrochloride, Xepin should be used with caution in patients with the following conditions: glaucoma, a tendency to urinary retention, severe liver disease, mania, or severe heart disease including those prone to cardiac arrythmias.

Cetyl alcohol may cause local skin reactions (e.g. contact dermatitis).

4.5 Interaction with other medicinal products and other forms of interaction

Alcohol ingestion may exacerbate the potential sedative effects of Xepin particularly in those individuals who use alcohol excessively. MAO inhibitors should be discontinued at least two weeks prior to the initiation of treatment with Xepin since serious interactions have been reported between orally administered doxepin hydrochloride and MAO inhibitors.

As doxepin is metabolised via hepatic microsomal enzymes, care should be taken when co-prescribing any other medicines which are also metabolised by this route.

Caution should also be exercised in patients being treated with cimetidine since it has been found to affect serum concentrations of orally administered tricyclic antidepressants, such as doxepin hydrochloride. Oral doxepin hydrochloride is known to interact with sympathomimetic agents and may increase the risk of arrythmias and hypotension or hypertentsion with general and local anaesthetics.

In view of the small but noteworthy amount of systemic absorption following topical administration of Xepin (see 5.2) caution should be exercised with these agents.

4.6. Pregnancy and Lactation

There is inadequate evidence of safety in human pregnancy and lactation. Reproductive studies performed in rats, rabbits, monkeys and dogs with oral doxepin showed no evidence of harm to the animal foetus.

As with all drugs, Xepin should only be used in pregnancy and lactation if, in the clinician's judgement, the benefits outweigh the risks.

4.7. Effects on Ability to Drive and Use Machines

Patients should be advised not to drive a motor vehicle or operate machinery whilst using Xepin. Particular caution should be exercised during the first few days of treatment.

4.8.    Undesirable Effects

Drowsiness has been reported in clinical trials, with an incidence of 12-19%. However, it is generally of mild to moderate severity and of short duration. Limiting the body surface treated to less than 10% is important in minimising the risk of drowsiness.

Local adverse reactions have been reported with the use of Xepin and may occur more frequently with the use of occlusive dressings. Local reactions, in decreasing order of frequency, include burning, stinging, irritation, and tingling and local rash. Systemic effects which have been observed with orally administered doxepin hydrochloride are rarely observed with topical Xepin. These may include anticholinergic effects (dry mouth, changes in taste, dry eyes, blurred vision, urinary retention); central nervous system effects other than drowsiness (headaches, fever, dizziness); and gastrointestinal effects (nausea, indigestion, vomiting and diarrhoea or constipation). Cases of suicidal ideation and suicidal behaviours have been reported during oral doxepin hydrochloride therapy or early after treatment discontinuation.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

4.9.    Overdose

Symptoms

Symptoms of overdosage of orally administered doxepin hydrochloride include an increase of any of the reported reactions, primarily excessive sedation and anticholinergic effects such as blurred vision and dry mouth. Other effects may be pronounced tachycardia, hypotension and extrapyramidal symptoms, but these are unlikely to be seen following topical use.

Treatment

Excess cream should be washed off immediately. Treatment of overdosage is essentially symptomatic. Supportive therapy may be necessary if hypotension and/or excessive sedation occur.

5 Pharmacological Properties

5.1. Pharmacodynamic Properties

Doxepin hydrochloride is a dibenzoxepin tricyclic compound structurally related to tricyclic antidepressant drugs such as amitriptyline. Doxepin hydrochloride has potent H₁ and H₂ receptor blocking actions.

Histamine is considered to be an important chemical mediator in the pathogenesis of pruritus. Histamine blocking drugs appear to compete at histamine receptor sites and inhibit the biological activation of histamine receptors.

5.2. Pharmacokinetic Properties

There is a small but noteworthy amount of systemic absorption following topical administration, with wide inter-individual variations in plasma levels and in the handling of doxepin. Orally administered doxepin undergoes extensive first-pass metabolism but topical administration avoids this initial clearance. Plasma doxepin levels following topical administration are generally low, although in a few subjects they may approach the lower limit of the therapeutic range (for depression) of orally administered doxepin.

5.3. Preclinical Safety Data

Doxepin, which is given orally as a tricyclic antidepressant, has been shown to have potent antihistamine activity in animal models. Acute and chronic toxicity of doxepin has been fully evaluated following oral administration to rats and dogs, and these studies revealed the expected effects for this class of drug.

The local toxicity of Xepin has been studied in healthy volunteers. It has been shown to be neither irritant nor allergenic, although it caused local irritation in a small number of cases.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Inactive ingredients in the cream are;

Sorbitol solution 70% (crystallising)

Ctyl alcohol, isopropyl myristate

glyceryl stearate

PEG 100 stearate

Wite soft paraffin

Bnzyl alcohol

Titanium dioxide E171

Purified water

6.2. Incompatibilities

None known.

6.3. Shelf Life

3 years.

6.4 Special precautions for storage

Do not store above 25°C

6.5. Nature and Contents of Container

Aluminium tubes with S-22 epoxyphenolic lining and a high density polyethylene spiked screw cap containing 30g, 60g or 120g Xepin A 6.0g pack is available as a professional sample.

Instruction for Use/Handling

Not applicable.

7 MARKETING AUTHORISATION HOLDER

Cambridge Healthcare Supplies Ltd

Unit 1 Chestnut Drive

Wymondham

Norfolk

NR18 9SB

8. MARKETING AUTHORISATION NUMBER

PL 16794/0008

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 06/09/2010

10 DATE OF REVISION OF THE TEXT

11/05/2015