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Naftidrofuryl Capsules Bp 100mg

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Naftidrofuryl Capsules BP 100mg

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each hard gelatin capsule contains 100mg Naftidrofuryl oxalate Ph.Eur.

3    PHARMACEUTICAL FORM

Pink hard gelatin capsules (size 2) printed “C” and “NL” in black.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Peripheral vascular disorders (intermittent claudication, night cramps, rest pain, incipient gangrene, trophic ulcers, Raynaud’s syndrome, diabetic arteriopathy and acrocyanosis).

4.2    Posology and method of administration

Posology

The capsules should be administered with a sufficient amount of water (one glass) during or after food.

Adults and the elderly

Peripheral vascular disorders: One or two 100mg capsules three times daily for a minimum of three months, or at the discretion of the physician.

In patients with renal impairment a dose adjustment may be considered.

Paediatric population

The safety and efficacy of naftidrofuryl in the paediatric population have not been established. This drug is not indicated for use in children.

Method of Administration For oral use (swallowing).

4.3    Contraindications

Known hypersensitivity to naftidrofuryl oxalate or other ingredients in the capsule.

Patients with a history of hyperoxaluria or recurrent calcium-containing stones.

4.4    Special warnings and precautions for use

The administration of Naftidrofuryl may modify the composition of the urine, promoting the formation of calcium oxalate kidney stones (the oxalate content is 19mg per 100mg of active ingredient).

Should be used with caution in patients with renal or hepatic disorders as the drug is metabolised in the liver and excreted mainly in the urine.

A sufficient amount of liquid should be taken during treatment to maintain an adequate level of diuresis.

The administration of Naftidrofuryl without liquid before going to bed may cause local oesophagitis. Therefore, it is essential to always take the capsule with a sufficient amount of water.

4.5    Interaction with other medicinal products and other forms of interaction

None known

4.6    Fertility, pregnancy and lactation

Pregnancy

In the absence of any relevant clinical data, the use of Naftidrofuryl is not advisable during pregnancy.

Lactation

In the absence of specific data concerning the excretion of the drug in human milk, Naftidrofuryl should not be used by breast-feeding women.

4.7    Effects on ability to drive and use machines

As Naftidrofuryl can cause dizziness patient should make sure they are not affected before driving or operating machinery.

4.8    Undesirable Effects

According to information collected during clinical trials and spontaneous reports since marketing authorisation, the following undesirable effects may occur under treatment with Naftidrofuryl.

The following definitions apply to the frequency terminology used hereafter:

very common >1/10

common >1/100, <1/10

uncommon >1/1,000, <1/100

rare >1/10,000, <1/1,000

very rare <1/10,000

frequency not known: cannot be estimated from the available data

Gastro-intestinal disorders:

Uncommon: Diarrhoea, nausea, vomiting and epigastric pain.

Frequency not known: In some patients who took the medicinal product without liquid before going to bed, the capsule being stuck in the throat led to local oesophagitis.

Renal and urinary disorders:

Very rare: Calcium oxalate kidney stones (see section 4.4).

Skin and subcutaneous tissue disorders:

Uncommon: Skin rash.

Hepatobiliary disorders:

Rare: Liver damage

Frequency not known: hepatitis and hepatic failure Central Nervous System

Frequency not known: dizziness, headache, agitation and sleep disorders. 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; website: www.mhra.gov.uk/yellowcard

4.9 Overdose

Signs and symptoms: Depression of cardiac conduction and convulsions may occur.

Treatment: The stomach should be emptied by gastric lavage and emesis. Activated charcoal may be employed if necessary. Cardiovascular function and respiration should be monitored and, in severe cases, electrical pacemaking or the use of isoprenaline should be considered. Convulsions may be managed with diazepam.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: peripheral vasodilator, ATC code: C04A X 21

Naftidrofuryl oxalate is a powerful vasodilator agent with an antagonist effect on 5-HT2 receptors of the smooth muscle cells. The vasodilator effect, which occurs in both the cerebral and peripheral circulation, is probably the main action. However, the drug has also been shown to activate intracellular aerobic metabolism as demonstrated by a reduction in the level of lactic acid level and an increased level of ATP. It is claimed that this action protects cells against the metabolic effects of ischaemia. Furthermore, naftidrofuryl oxalate is a powerful spasmolytic agent.

5.2    Pharmacokinetic properties

Peak plasma levels are attained at 0.5-0.75 hours after oral dose. Some 24% of the drug (range 17-32%) is absorbed from the gastrointestinal tract. There is some pre-systemic metabolism. The plasma half life is approximately 1 hour (range 0.8-1.6 hours). The drug penetrates brain and other tissues. It is, however, 80% bound to albumin. Cumulation does not occur at a dose level of 200mg three times daily. Naftidrofuryl oxalate is excreted principally via the urine, all in the form of metabolites.

5.3    Preclinical safety data

No toxic effects were seen in animal studies which provide additional information to that obtained in man. In repeated dose studies the no effect level was 25mg/kg/day or greater. There was no evidence of effects on reproduction below doses which caused maternal toxicity.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

The capsule contains:

Maize starch

Microcrystalline cellulose (E460)

Sodium starch glycollate Colloidal silica Stearic acid Magnesium stearate

The capsule shell contains:

Erythrosine (E127)

Titanium dioxide (E171)

Gelatin

The printing ink contains:

Shellac (E904)

Propylene glycol (E1520)

Iron oxide black (E172)

Potassium hydroxide (E525)

6.2    Incompatibilities

None known

6.3    Shelf life

Shelf-life

Two years from the date of manufacture.

Shelf-life after dilution/reconstitution Not applicable.

Shelf-life after first opening Not applicable.

6.4    Special precautions for storage

Store below 25°C in a dry place.

Protect from light.

6.5    Nature and contents of container

The product containers are rigid injection moulded polypropylene containers with snap-on polyethylene lids.

The product may also be supplied in blister packs in cartons:

a)    Carton: Printed carton manufactured from white folding box board.

b)    Blister pack: (i) 250pm white rigid PVC/PVdC.

(ii) Surface printed 20pm hard temper aluminium foil with 5-7g/M2 PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes

Al/PVC/PVDC: 28s, 30s, 56s, 60s, 84s, 90s, l00s, 112s, 120s, 168s, 180s PP Tablet Container: l00s, 250s, 500s, l000s

6.6    Special precautions for disposal

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Actavis UK Limited (Trading style: Actavis)

Whiddon Valley BARNSTAPLE North Devon EX32 8NS

8    MARKETING AUTHORISATION NUMBER(S)

PL 00142/0429

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22/12/1998 / 30/01/2004

10    DATE OF REVISION OF THE TEXT

04/11/2015