PAROEX 1.2 MG / ML MOUTHWASH - summary of medicine characteristics

Paroex 1.2 mg/ml, mouthwash

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml contains 1.2 mg chlorhexidine digluconate

Excipients with known effect: azorubine (E122), macrogolglycerol hydroxystearate, propyleneglycol

For the full list of excipients see Section 6.1.

3 PHARMACEUTICAL FORM

Mouthwash

A clear, red coloured liquid with an odour and flavour of menthol.

4.1 Therapeutic indications

Adjunctive treatment of oral mucosa infections and post-operative care in stomatology.

4.2 Posology and method of administration

Posology

15 ml of solution is used one to three times a day.

Paroex 1.2 mg/ml, mouthwash would normally not be used for more than 5 days at a time. It may be used over a longer period of time if advised by the dentist or the physician.

Paediatric population

Children under 6 years should only use Paroex 1.2 mg/ml, mouthwash after consultation with a doctor or dentist.

Method of administration:

Paroex 1.2 mg/ml, mouthwash is ready to use and must not be diluted.

Use preferably after meals and after teeth have been brushed and the oral cavity rinsed thoroughly with water.

Fill the cap up to the marking ring (15 ml); rinse for 1 minute in the mouth; spit out, do not swallow and do not post-rinse. If the presentation does not include a dosing cup, use a table spoon (15 ml).

4.3 Contraindications

Paroex 1.2 mg/ml, mouthwash should not be used in the case of hypersensitivity to chlorhexidine bis (D-gluconate), or any of the excipients.

4.4 Special warnings and precautions for use

For oromucosal use only – should be kept out of the eyes and ears, or other tissues except the oral mucosa. If the mouthwash comes into contact with the eyes, it should be washed out promptly and thoroughly with plenty of water.

In the case of ulcerations and erosive-desquamative exfoliation of the oral mucosa, the medicinal product should not be used.

Continuous use could modify the oral microbial flora, this being associated with the risk of bacterial and fungal spreading (candidiasis). If symptoms persist after 5 days and/or are associated with fever, therapeutic options should be reconsidered.

Chlorhexidine digluconate may cause acute allergic reactions including anaphylaxis (see section 4.8).

Azorubine (E122) may cause allergic reactions.

Macrogolglycerol hydroxystearate may cause skin reactions. In case of accidental ingestion, it may cause stomach upset and diarrhoea.

Propyleneglycol may cause skin irritation.

4.5 Interaction with other medicinal products and other forms of interaction No interactions with other medicinal products are known.

The efficacy of Paroex 1.2 mg/ml, mouthwash is reduced by anionic substances which are generally ingredients of conventional toothpastes. Paroex 1.2 mg/ml should therefore be used after teeth have been brushed and the oral cavity rinsed thoroughly with water.

Immediately after the use of Paroex 1.2 mg/ml, mouthwash sugary foods and drinks should not be consumed, otherwise the efficacy would be reduced.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of Chlorhexidine digluconate in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of Paroex 1.2 mg/ml during pregnancy.

Lactation

It is unknown whether Chlorhexidine digluconate /metabolites are excreted in human milk. As a precautionary measure, it is preferable to avoid the use of Paroex 1.2 mg/ml during lactation.

Fertility

No human data on the effect of Chlorhexidine digluconate on fertility are available. In rats, there was no effect on mating or fertility with Chlorhexidine digluconate treatment (see section 5.3).

4.7 Effects on ability to drive and use machines

Paroex 1.2 mg/ml, mouthwash has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The frequency of side effects is classified according to the following categories: 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

In rare cases (< 0.1%), increased tartar formation may occur.

Rarely, hypersensitivity reactions may occur.

In isolated cases, severe allergic reactions have also been reported with symptoms such as bronchospasm, dyspnoea, periorbital oedema, hypotension and shock, including anaphylaxis after local application of chlorhexidine.

In rare cases (< 0.1%), regular use may lead to bleeding of gums after brushing teeth.

In very rare cases (< 0.01%), reversible desquamative changes in the mucosa may occur.

In very rare cases (< 0.01%), irritation of the oral mucosa may occur.

With oral administration, reversible discoloration of hard dental tissues, restorations and lingual papillae (glossotrichia) may occur. Brownish discoloration of the teeth may occur.

By reducing the consumption of tea, coffee and red wine, these symptoms can be prevented.

Wound healing disorders are possible.

At the start of treatment, a burning sensation on the tongue may occur. The following may also occur: Reversible impairment of taste sensation, reversible numbness of the tongue.

These symptoms generally improve over the course of use of Paroex 1.2 mg/ml, mouthwash. If the symptoms still persist after cessation of treatment, consult a doctor or pharmacist.

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 Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9 Overdose

When used as directed, the amounts of chlorhexidine resorbed by the mucous membrane can be detoxified by the human body without toxic signs. Therapeutic measures for detoxification

are not necessary. In local overdose, Paroex 1.2 mg/ml, mouthwash can be eliminated by rinsing with water. In case of accidental contact with the eyes, the eye area or the ear canal, rinse with copious amounts of water. No data exists on acute oral toxicity in humans; however, from experiments on rats, we can extrapolate an LD50 of around 1,400 g of solution for an average adult (70 kg).

Ingestion of 30 or 60 ml by a young child (10 kg) may cause stomach upset and vomiting.

In addition, this medicine contains terpene derivatives as excipients, which may lower the seizure threshold and lead at high doses to neurological injuries in children (convulsions) and elderly subjects (agitation and confusion). Respect the posology and the recommended duration of treatment (see section 4.2).

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-infectives and antiseptics for local oral treatment, ATC code: A01AB03

Chlorhexidine is a base and is therefore most stable in the salt form. The free base, the diacetate and dihydrochloride have only slight solubility in water (0.08, 1.0 and 0.06 g/100 ml respectively), while the digluconate has very high solubility in water (>50 g/100 ml).

Therefore, the digluconate is generally used for various indications.

Chlorhexidine and its salts exhibit a broad antimicrobial activity against Grampositive and Gram-negative bacteria.

The activity against some Gram-negative bacteria (Pseudomonas and Proteus species) and against yeasts, dermatophytes and mycobacteria is low. It is ineffective against bacterial and fungal spores, viruses and putrefactive fungi.

The mean inhibitory concentrations (jrg/ml) are:

Bacteria:

Escherichia coli

Salmonella spp.

Enterobacter

Klebsiella spp.

Serratia marcescens

Proteus sp.

Pseudomonas aeruginosa

Streptococcus mutans

ß-haemolytic streptococci

Staphylococcus aureus

Streptococcus faecalis

Yeasts, dermatophytes and moulds:

Candida albicans

Microsporum canis

Aspergillus versicolor

Chlorhexidine works most effectively at neutral and slightly alkaline pH values. In the acidic pH range, its efficacy is reduced.

In the presence of soaps, blood or pus (cell fragments), the efficacy of chlorhexidine is reduced (100 – 1000-fold higher inhibitory concentrations required).

Mouth rinsing with 10 ml of a 0.2% chlorhexidine solution leads to a strong reduction of the salivary bacterial count detectable for up to 12 hours. This is also correlated with a reduced rate of formation of dental plaque. When used over several months, the effect decreases due to a reversible shift in the bacterial spectrum of oral flora and dental plaque. There are no studies regarding the consequences of a shift in the oral bacterium spectrum.

5.2 Pharmacokinetic properties

After repeated use of chlorhexidine on healthy skin, no resorbed amounts of substance could be detected in adults. However, on bathing premature and new-born infants (28 – 39 gestation weeks) in 4% chlorhexidine digluconate detergent solution, small amounts of up to 1.0 jig/ml of this substance were detectable in the blood (no clinical symptoms; haemolysis occurred in vivo in combination with other disinfectants at concentrations > 20 jig/ml).

After oral application of chlorhexidine, high activities were found in the digestive tract of rats and mice. Resorption occurred at a slow rate.

Chlorhexidine is adsorbed in enamel, dentin, cement, dental pellicle, mucous membranes and restorations. Due to slow desorption, chlorhexidine is detectable in saliva for up to 8 hours (depot effect). The resorption of chlorhexidine via the intact oral mucosa is not known. The excretion of chlorhexidine in various experimental animals occurs mainly via faeces (90%). In human trials, the elimination half-life was 4 days.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction and development.

6.1

Glycerol,

Sucralose,

Macrogolglycerol hydroxystearate,

Propylene glycol,

Azorubine (E 122),

Optamint flavour*, Purified water.

*Composition of the flavour: menthol, anethole, eucalyptol, peppermint oil, menthone, menthyl acetate, racemic menthol, propylene glycol, triacetin, star anise essential oil, geranium essential oil, vanillin, maltol, oil mandarin essential, ethanol.

6.2 Incompatibilities

Chlorhexidine is incompatible with soaps and other anionic substances.

At concentrations above 0.05%, chlorhexidine forms salts with borates, dicarbonates, carbonates, chlorides, citrates, phosphates and sulphates, which may crystallise out.

At concentrations below 0.01%, crystallisation of salts is not expected.

Chlorhexidine is inactivated by sucrose.

Chlorhexidine may be inactivated by polysorbate-80, insoluble magnesium, zinc and calcium salts.

6.3 Shelf life

2 years

Expires 1 month after opening (50, 100, 300 and 500 ml)

Expires 3 months after opening (5 l)

6.4 Special precautions for storage Not applicable.

6.5 Nature and contents of container

50 ml polyethylene terephthalate bottle with polyethylene cap

100 ml polyethylene terephthalate bottle with polyethylene cap and polypropylene dosing cup

300 ml polyethylene terephthalate bottle with polyethylene cap and polypropylene dosing cup 500 ml polyethylene terephthalate bottle with polyethylene cap and polypropylene dosing cup

5000 ml polyethylene terephthalate bottle with polyethylene cap and polyethylene dosing pump

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

SUNSTAR FRANCE

55/63 rue Anatole France

92300 LEVALLOIS PERRET

FRANCE

8 MARKETING AUTHORISATION NUMBER(S)

PL 47517/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

06/09/2017/10­/09/2020