Document: spc-doc_PL 05536-0001 change

• spc-doc_PL 05536-0001
• spc-doc_PL 27682-0002

---

SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Octenidine dihydrochloride / Phenoxyethanol 1 mg/ml + 20 mg/ml cutaneous spray, solution

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml solution contains:

Octenidine dihydrochloride    1 mg

Phenoxyethanol    20 mg

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Cutaneous spray, solution

Clear, colourless, almost odourless solution

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Octenidine dihydrochloride / Phenoxyethanol is indicated for repeated shortterm antiseptic treatment of mucous membranes and adjacent tissues prior to diagnostic procedures in the anogenital region including the vagina, vulva and glans penis as well as prior to bladder catheterization.

Octenidine dihydrochloride / Phenoxyethanol is also indicated for antiseptic treatment of small superficial wounds and skin disinfection prior to nonsurgical procedures.

Octenidine dihydrochloride / Phenoxyethanol may be used in patients of all age groups.

4.2 Posology and method of administration

The solution is intended for cutaneous use.

Octenidine dihydrochloride / Phenoxyethanol is applied to the area to be treated until complete moistening is achieved. Following application and prior to further measures, such as e.g. the application of a wound dressing, an exposure time of at least 1 to 2 minutes must be observed.

These instructions must be carefully followed in order to achieve the desired effect.

So far there is only experience of continuous use for no longer than 14 days, therefore Octenidine dihydrochloride / Phenoxyethanol should only be used for a limited treatment period.

Paediatric population

The posology of Octenidine dihydrochloride / Phenoxyethanol is identical in adults and children.

4.3 Contraindications

Octenidine dihydrochloride / Phenoxyethanol must not be used in cases of hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

Octenidine dihydrochloride / Phenoxyethanol must not be used for rinses in the abdominal cavity (e.g. intra-operatively) or the bladder, nor on the tympanic membrane.

4.4 Special warnings and precautions for use

Do not allow Octenidine dihydrochloride / Phenoxyethanol to pass into the circulation, e.g. as a result of accidental injection.

4.5 Interaction with other medicinal products and other forms of interaction

Do not use Octenidine dihydrochloride / Phenoxyethanol concomitantly with PVP iodine-based antiseptics on adjacent areas of skin, as strong brown to violet discolorations can occur at the border areas.

The incompatibility of the medicine in the concomitant use with anionic surfactants (soap, detergent, etc) can reduce or nullify its activity.

4.6 Pregnancy and lactation

Pregnancy

There is a moderate amount of data (between 300 - 1000 pregnancy outcomes, gestational age > 12 weeks) from the use of octenidine dihydrochloride / phenoxyethanol combinations in pregnant women. No adverse events have been reported during and after birth. Animal studies with octenidine dihydrochloride do not indicate reproductive toxicity (see section 5.3). Animal studies with dermal application of 2-phenoxyethanol do not indicate reproductive toxicity (see section 5.3).

The use of Octenidine dihydrochloride / Phenoxyethanol may be considered during pregnancy, if necessary.

Lactation:

There are no adequate experimental animal and clinical data on the use of Octenidine dihydrochloride / Phenoxyethanol during lactation. As octenidine dihydrochloride is only absorbed in very small amounts or not at all, it must be assumed that it does not pass into breast milk.

Phenoxyethanol is absorbed rapidly and almost completely. There are no data regarding the excretion of phenoxyethanol in breast milk. As a precaution, Octenidine dihydrochloride / Phenoxyethanol should not be applied in the area of the breast during the nursing period.

Fertility

There are no human data regarding the effect of octenidine and phenoxyethanol on fertility. Octenidine did not affect fertility in rats and rabbits. Phenoxyethanol did not affect fertility in mice.

4.7 Effects on ability to drive and use machines

Octenidine dihydrochloride / Phenoxyethanol has no influence on the ability to drive and use machines.

4.8 Undesirable effects

The evaluation of undesirable effects is based on the following rates of occurrences:

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)

General disorders and administration site conditions

Rare: burning, redness, itching and warmth at the application site

Very rare: allergic contact reaction, e.g. temporary redness at the application

site

Paediatric population

Frequency, type and severity of adverse reactions in children are the same as in adults.

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

There is no knowledge of cases of overdose. However, overdosing of a topical preparation is very unlikely. In the case of local overdose, the affected areas can be rinsed with plenty of Ringer’s solution.

Accidental oral ingestion of Octenidine dihydrochloride / Phenoxyethanol is not considered dangerous as acute toxicity of octenidine hydrochloride and 2-phenoxyethanol via oral administration route is low (section 5.3). However, in cases of oral ingestion of larger amounts of Octenidine dihydrochloride / Phenoxyethanol irritation of the mucosa of the gastrointestinal tract cannot be ruled out.

The acute toxicity of octenidine hydrochloride and 2-phenoxyethanol via intravenous administration route is low (section 5.3). Taking the low concentrations of the active substances into account an intoxication appears very unlikely. However, Octenidine dihydrochloride / Phenoxyethanol should

not be allowed to pass into the circulation, e.g. as a result of accidental injection.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiseptics and disinfectants / Quaternary ammonium compounds / octenidine, combinations

ATC code: D08AJ57

Mechanism of action

Octenidine dihydrochloride is a cation-active compound and as a result of its two cationic centres possesses marked surface-active properties. It reacts with cell wall and membrane components of the microbial cell and thus leads to destruction of cell function.

The mechanism of antimicrobial action of phenoxyethanol is based, among other effects, on an increased permeability of the cellular membrane for potassium ions.

Pharmacodynamic properties

Octenidine dihydrochloride / Phenoxyethanol displays the following range of in vitro efficacy:

•    Gram-positive and Gram-negative bacteria

•    Yeasts and fungi

Octenidin dihydrochloride / Phenoxyethanol meets the criteria for chemical disinfectants and antiseptic products as established by European Standards:

•    EN 1040 - basic bactericidal activity (Phase 1)

•    EN 1275 - basic yeasticidal activity (Phase 1)

•    EN 13727 - bactericidal activity (Phase 2/step 1)

•    EN 13624 - fungicidal activity (Phase 2/step 1)

The spectra of efficacy of phenoxyethanol and octenidine dihydrochloride complement each other in this respect. Specific primary resistance to octenidine dihydrochloride / phenoxyethanol combinations and the formation of secondary resistance in cases of prolonged use as a result of its non-specific efficacy are not to be expected.

Table: in vitro microbiocidal efficacy against exemplary germs

Strain	Contact time	Concentration tested	Conditions	Result	EN criteria
Staphylococcus aureus	0.5 min	90%	10% bovine albumin	6.14 log reduction	EN 13727
	0.5 min		4.5%	6.06 log

			defibrinated sheep blood, 4.5% bovine albumin, 1% mucin	reduction
Enterococcus faecalis	0.5 min	90%	10% bovine albumin	6.51 log reduction	EN 13727
	0.5 min		4.5% defibrinated sheep blood, 4.5% bovine albumin, 1% mucin	6.68 log reduction
Pseudomonas aeruginosa	0.5 min	90%	10% bovine albumin	6.85 log reduction	EN 13727
	1.0 min		4.5% defibrinated sheep blood, 4.5% bovine albumin, 1% mucin	6.13 log reduction
Escherichia coli	0.5 min	90%	10% bovine albumin	6.26 log reduction	EN 13727
	1.0 min		4.5% defibrinated sheep blood, 4.5% bovine albumin, 1% mucin	5.63 log reduction
Candida albicans	10 min	90%	10% bovine albumin	5.95 log reduction	EN 13624
	10 min		4.5% defibrinated sheep blood, 4.5% bovine albumin, 1% mucin	5.39 log reduction
Aspergillus brasiliensis	20 min	80%	n/a	4.8 log reduction	EN1275

Paediatric population

The efficacy and tolerability of the octenidine dihydrochloride / phenoxyethanol combination was demonstrated in 347 children aged 6 days to 12 years, as well as 73 premature infants with a gestational age of less than 36 weeks.

Treatment of the umbilical stump with an octenidine dihydrochloride / phenoxyethanol combination was studied in 1725 newborns demonstrating tolerability in this age group.

5.2 Pharmacokinetic properties

Absorption

Orally administered ¹⁴C-radioactively labelled octenidine dihydrochloride was absorbed only in very small amounts (0 - 6%) via the mucous membranes of the gastrointestinal tract in mouse, rat and dog. In mouse it was found that topically applied amounts of octenidine dihydrochloride were not absorbed during a 24-hour contact time under an occlusive dressing.

On the basis of in vitro studies, passage of octenidine dihydrochloride across the placenta can be ruled out.

Octenidine dihydrochloride was not absorbed either via the mucous membrane of the vagina (rabbit) or via wounds (humans, rat).

Orally administered ¹⁴C-phenoxyethanol is absorbed almost completely and is excreted with the urine in the form of phenoxyacetic acid.

Paediatric population

The oxidative metabolism of 2-phenoxyethanol was studied in 4 babies aged 1 week to 11 months, as well 24 premature infants with a gestational age of less than 36 weeks. It was shown that 2-phenoxyethanol is absorbed via the skin and completely or almost completely metabolised by oxidation to phenoxyacetic acid and eliminated via the kidneys.

5.3 Preclinical safety data

Non-clinical data from acute and repeated dose toxicity studies, as well as from reproductive toxicology, genotoxicity and carcinogenicity studies with octenidine revealed no specific hazard for humans at the intended therapeutic doses.

Non-clinical data from acute and repeated dose toxicity studies and from genotoxicity studies with phenoxyethanol revealed no specific hazard for humans at the intended therapeutic doses.

A study in which mice were treated with phenoxyethanol via the diet over the whole reproduction cycle revealed a decreased pup body weight after birth and during lactation and increased pup lethality during lactation. Because the results were obtained following oral administration, its clinical relevance is not clear. In a dermal embryofoetal development study with phenoxyethanol in rabbits no adverse effects were found.

Phenoxyethanol was slightly irritating to rabbit skin.

No carcinogenicity studies were performed with phenoxyethanol.

The combination of octenidine and phenoxyethanol was slightly irritating to rabbit eyes.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Cocamidopropylbetaine sodium gluconate glycerol 85 % sodium chloride

sodium hydroxide solution (10 %) purified water

6.2    Incompatibilities

With anionic surfactants, e.g. from detergents and cleaning preparations the octenidine cation can form insoluble complexes, which can reduce or nullify its activity.

6.3    Shelf life

250 ml:5 years 50 ml:3 years

After first opening: use within 1 year.

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

Nature and contents of container

50ml: white moulded bottle of polyethylene (high density) provided with a white tamper proof manual spray pump of polyethylene (low density) and polypropylene packed in a folding box containing 50 ml of medicinal product

250ml: white round bottle of polyethylene (high density) provided with a white tamper proof manual spray pump of polyethylene (low density) and polypropylene containing 250 ml of medicinal product

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

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

7    MARKETING AUTHORISATION HOLDER

Schulke & Mayr GmbH Robert-Koch Str. 2 22851 Norderstedt Germany

8    MARKETING AUTHORISATION NUMBER(S)

PL 05536/0001

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 12/08/2015

19/09/2016