SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

STIMLOR

Naftidrofuryl oxalate 100 mg capsules.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 100 mg of Naftidrofuryl Oxalate. For excipients see 6.1.

3 PHARMACEUTICAL FORM

Capsule, hard.

Rose coloured capsule containing a white powder and overprinted 2N1.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Naftidrofuryl oxalate may be used to treat peripheral and cerebral vascular disorders. Naftidrofuryl oxalate is indicated for the following peripheral vascular disorders: rest pain, night cramps, intermittent claudication, incipient gangrene, Raynaud’s syndrome, trophic ulcers, diabetic arteriopathy and acrocyanosis; and for the following cerebral vascular disorders: cerebral atherosclerosis and cerebral insufficiency, particularly where manifest as confusion and mental deterioration in the elderly.

4.2 Posology and method of administration

For oral administration. The capsules should be swallowed whole during meals with a sufficient amount of water - minimum of one glass.

Adults:

Peripheral vascular disorders:    100 mg to 200 mg taken three times a day for

a minimum period of three months or at the discretion of the physician.

Cerebral vascular disorders:    100 mg three times a day for a minimum

period of three months or at the discretion of the physician.

Children:    Naftidrofuryl oxalate is not recommended for

use in children.

The Elderly:    The usual adult dose is appropriate.

4.3 Contraindications

Naftidrofuryl oxalate capsules are contra-indicated for use in patients with known hypersensitivity to naftidrofuryl oxalate and those with a history of hyperoxaluria or recurrent calcium-containing stones.

4.4 Special warnings and precautions for use

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

In order to maintain an adequate level of diuresis, a sufficient amount of liquid should be taken during treatment.

The administration of naftidrofuryl oxalate 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 Pregnancy and lactation

Pregnancy

There is no, or inadequate, evidence as to the safe use of naftidrofuryl oxalate in human pregnancy. Naftidrofuryl oxalate has been widely used for many years without apparent ill consequence, animal studies having shown no hazard. If drug therapy is required in pregnancy, naftidrofuryl oxalate can be used in the absence of a safer alternative.

Lactation

There is no information available regarding use in lactation.

Effects on ability to drive and use machines

None known.

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 oxalate.

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.

4.9 Overdose

Symptoms:    depression of cardiac conduction, convulsions.

Procedures:    empty the stomach by gastric lavage and emesis. If necessary,

activated charcoal may be used. Monitor cardiovascular function and respiration. In severe cases, electrical pacemaking or the use of isoprenaline should be considered. Convulsions may be controlled by diazepam.

5.1    Pharmacodynamic properties

ATC Code: C04A X21 (other peripheral vasodilators)

Naftidrofuryl oxalate is used in the treatment of peripheral and cerebral vascular disorders.

It has been shown to exert a direct effect on intracellular metabolism. Thus it has been shown in man and animals that it produces an increase of ATP levels and a decrease of lactic acid level in ischaemic conditions, evidence for an enhancement of cellular oxidative capacity. Furthermore, naftidrofuryl oxalate is a powerful spasmolytic agent.

5.2    Pharmacokinetic properties

Naftidrofuryl oxalate is well absorbed when given orally. Peak plasma levels are attained at 0.5 - 0.75 hours after an oral dose. There is some pre-systemic metabolism. 24% of drug (range 17-32%) is absorbed from the gastrointestinal tract. The plasma half-life is approximately 1 hour, although inter subject variation is relatively high (range 0.8-1.6 hours). Accumulation does not occur at a dose level of 200 mg three times daily.

The drug becomes extensively bound to plasma proteins and 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 25 mg/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

Capsule contents:

maize starch,

povidone (E1201),

sodium lauryl sulphate,

talc (E553(b)),

sodium starch glycollate,

colloidal silicon dioxide (E551),

magnesium stearate (E572),

stearic acid (E570).

Capsule shell: gelatin,

azorubine (E122), titanium dioxide (E171).

Printing ink:

Shellac

Propylene glycol (E1520) Black iron oxide(E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

30 months.

6.4 Special precautions for storage

Store below 25° C. Store in original package.

6.5 Nature and contents of container

HDPE or polypropylene containers with caps or child resistant closures in packs of 28, 30, 50, 56, 60, 90, 100, 250, 500 or 1000 capsules.

Blister strips in packs of 10, 28, 30, 56, 84, 90, 100 or 500 capsules.

Glass jar with screw cap containing 90, 100 or 500 capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Not applicable.

7    MARKETING AUTHORISATION HOLDER

TEVA UK Limited,

Brampton Road Hampden Park Eastbourne East Sussex BN22 9AG

8    MARKETING AUTHORISATION NUMBER(S)

PL 00289/0240

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

04/10/1995 / 07/06/2006

10 DATE OF REVISION OF THE TEXT

30/06/2013