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Britlofex Tablets 0.2mg

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

BritLofex Tablets 0.2mg

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Lofexidine hydrochloride 0.2mg

3.    PHARMACEUTICAL FORM

Film-coated tablets.

Peach coloured, round tablet

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

To relieve symptoms in patients undergoing opioid detoxification.

4.2    Posology and method of administration

The recommended route of administration is by mouth.

ADULTS

The dosage of lofexidine should be titrated according to the patient's response. Initial dosage should be 0.8mg per day in divided doses. The dosage may be increased by increments of 0.4 to 0.8mg per day up to a maximum of 2.4mg daily. Maximum single dose should not exceed 4 x 0.2mg tablets (0.8mg). Each patient should be assessed on an individual basis; those undergoing acute detoxification will usually require the highest recommended dose and dosage increments to provide optimum relief at the time of expected peak withdrawal symptoms.

In cases where no opioid use occurs during detoxification, a duration of treatment of 7-10 days is recommended. In some cases the physician may consider longer treatment is warranted.

CHILDREN:

Safety and effectiveness in children has not been established.

ELDERLY:

There is no experience of dosing in the elderly from clinical studies. Should use in the elderly be necessary it is advised that special caution is observed in the presence of heart disease or anti-hypertensive therapy.

4.3. Contraindications

BritLofex tablets are contraindicated in patients who are allergic to lofexidine or to other imidazoline derivatives or to any excipients of BritLofex.

4.4 Special warnings and precautions for use

As with other hypotensive agents, therapy with lofexidine should not be discontinued abruptly. Dosage should be reduced gradually over a period of 2-4 days or longer, to minimise blood pressure elevation and associated signs and symptoms. Lofexidine should be used with caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease or chronic renal failure and in patients with bradycardia or hypotension. Blood pressure and pulse rate should be assessed frequently. Patients with a history of depression should be carefully observed during long-term therapy with lofexidine.

There have been reports of QT prolongation during lofexidine treatment. Whilst the nature of the relationship between lofexidine and these ECG changes is not yet clear, it would be prudent to avoid the use of lofexidine in patients at risk of QT prolongation i.e. those with known QT problems, metabolic disturbances, pre-existing cardiovascular disease, relevant family history or those taking other drugs known to prolong the QT interval.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Allergic reactions may occur due to the presence of E110 (Sunset Yellow).

4.5 Interaction with other medicinal products and other forms of interaction

Lofexidine may enhance the CNS depressive effects of alcohol, barbiturates and other sedatives.

Lofexidine may enhance the effects of anti-hypertensive drug therapy.

Concomitant use of tricyclic antidepressants may reduce the efficacy of lofexidine.

Concomitant use of drugs which prolong the QT interval or cause electrolyte imbalance should be avoided.

4.6 Fertility, pregnancy and lactation

Pregnancy:

The safety of lofexidine in pregnant women has not been established. High doses of lofexidine given to pregnant dogs and rabbits caused a reduction in foetal weight and increased abortions. Lofexidine should only be administered during pregnancy if the benefit outweighs the potential risk to mother and foetus.

Breast-feeding:

It is not known whether this drug is excreted in human milk and caution should be exercised when it is administered to a nursing woman.

4.7. Effects on ability to drive and use machines

Lofexidine may have a sedative effect. If affected, patients should be advised not to drive or operate machines.

4.8 Undesirable effects

The adverse effects of the drug are primarily related to its central alpha-adrenergic agonist effects:

Very common (>1/10)

Common (>1/100 to <1/10)

Uncommon (>1/1,000 to <1/100)

Rare (>1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Immune system disorders:

Not known:

Allergic reactions may occur due to the presence of E110 (Sunset Yellow). Nervous system disorders:

Very common:

Dizziness has been reported following treatment with lofexidine.

Drowsiness and related symptoms including sedation and somnolence have been reported.

Cardiac disorders:

Very common:

Bradycardia has been reported.

Not known:

There have been reports of QT prolongation during lofexidine treatment. Vascular disorders:

Very common:

Hypotension has been reported.

General disorders and administration site conditions:

Very common:

Dryness of mucous membranes especially the mouth, throat and nose has been reported.

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 national reporting system listed below:

Yellow Card Scheme

Website: www.yellowcard.mhra.gov.uk/

4.9. Overdose

Overdosage may cause hypotension, bradycardia and sedation. Gastric lavage should be carried out where appropriate. In most cases, all that is required are general supportive measures.

5. Pharmacological Properties

5.1. Pharmacodynamic properties

Lofexidine hydrochloride is an orally active imidazoline adrenergic alpha-2-receptor agonist; and is believed to have a high affinity for 2A receptor subtypes resulting in less anti-hypertensive activity than clonidine, a nonselective alpha-2-receptor agonist. Hypotension may occur in susceptible subjects, accompanied by a decrease in heart rate.

Abrupt discontinuation of lofexidine has been, in some cases, associated with a transient increase in blood pressure to higher-than-pre-treatment levels.

5.2. Pharmacokinetic properties

Lofexidine is extensively absorbed and achieves peak plasma concentration at 3 hours after administration of a single dose. The elimination half-life is 11 hours with accumulation occurring up to four days with repeat dosing. Lofexidine undergoes extensive metabolism in the liver and excretion is mainly by the kidney.

5.3. Preclinical safety data

Animal toxicology. Lofexidine was tolerated at high dosage in singe dose toxicity studies in animals, the LD50 being >77mg/kg. With repeat dosing in mice, rats and dogs symptoms related to the pharmacology of the drug (ataxia, sedation, tremor, unkempt appearance and exhaustion) appeared.

Studies of mutagenicity are incomplete but lofexidine did not display mutengenicity in the Ames test. Long term studies in rats showed no evidence of carcinogenicity.

High doses lofexidine given to pregnant rats and rabbits caused a reduction in the foetal weight and increased abortions. No teratogenic effects were found.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose (monohydrate) Citric Acid Povidone

Microcrystalline Cellulose Calcium Stearate Sodium Lauryl Sulphate Purified Water

Film Coat:

Opadry OP-S-9480 Brown

Containing

Hydroxypropylmethyl cellulose Titanium dioxide Propylene glycol Indigo Carmine (E132)

Sunset yellow (E110)

6.2. Incompatibilities

None known

6.3 Shelf life

24 months

6.4. Special Precautions for Storage

Store below 25°C. Store in the original package.

6.5. Nature and Contents of Container

Amber glass bottles or high density polyethylene bottles or blister strips.

6.6 Special precautions for disposal

No special instructions.

7    MARKETING AUTHORISATION HOLDER

Britannia Pharmaceuticals Limited

Park View House

65 London Road

Newbury

Berkshire

RG14 1JN

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 04483/0036

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12 October 1990

10    DATE OF REVISION OF THE TEXT

02/01/2015