AT/H/0661/001/DC, final SmPC

SUMMARY OF PRODUCT CHARACTERISTICS

[Invented name] 4 mg/g + 25 mg/g ointment 1 AT/H/0661/001/DC, final SmPC

1. NAME OF THE MEDICINAL PRODUCT

[Invented name] 4 mg/g + 25 mg/g ointment

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 g ointment contains 4 mg nonylic acid vanillylamide (nonivamide) and 25 mg β-butoxyethylester of nicotinic acid (nicoboxil).

Excipient(s) with known effect 1 g ointment contains 2 mg sorbic acid. Fragrance with with α-Isomethyl ionone, α-Amylcinnamaldehyde, α-Amylcinnamyl alcohol, Anisyl alcohol, Evernia furfuracea extract (Treemoss extract), Benzyl alcohol, Benzyl benzoate, Benzyl cinnamate, Benzyl salicylate, Citral, Citronellol, Coumarin, Oakmoss extract, , Farnesol, , α-Hexylcinnamaldehyde, , Isoeugenol, Butylphenyl methylpropional (Lilial), Limonene, , Hydroxyisohexyl 3-Cyclohexene Carboxaldehyde (Lyral), Methyl heptane carbonate, , Cinnamyl alcohol . (see section 4.4)

Benzyl alcohol: less than 0.002 mg/100g (see section 4.4)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Ointment

Almost white or slightly yellowish, opaque, smooth homogeneous ointment with odour of citronella oil.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

To stimulate blood flow in the skin for treating muscle and joint complaints.

For treatment of acute low back pain with no signs of neuropathic origin.

To stimulate blood flow in the skin before taking a capillary blood sample, e.g. from the earlobe or the digital pulp.

4.2 Posology and method of administration

Posology

Treatment should start with a very small quantity and on a very small skin area to test individual reaction. Response to [Invented name] 4 mg/g + 25 mg/g ointment varies and some people only need a very small amount to generate a warming feeling while others might experience very little or no warming effect.

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Starting dose should be not more than ½ cm ointment (about the size of a pea) for an area the size of the palm. Even small amounts produce a noticeable effect of warming, which occurs a few minutes after application and develops its maximum effect during 20-30 minutes.

At the following applications the dose can be intensified, corresponding to the individual tolerance. Maximum recommended dose per application should be 1 cm of ointment for an area the size of 1 palm. [Invented name] 4 mg/g + 25 mg/g ointment should be used when needed, up to 2-3 times per day. The maximum daily dose should not exceed 3 applications.

Paediatric population The safety and efficacy of [Invented name] 4 mg/g + 25 mg/g ointment has not been established in children and adolescents under 18 years.

Method of administration For cutaneous use The ointment should be spread lightly over the painful area, using the enclosed applicator and should be spread with the hand until only a slight gloss can be seen on the skin. After using [Invented name] 4 mg/g + 25 mg/g ointment hands should be washed thoroughly with soap and water.

To stimulate blood flow in the skin before taking a capillary blood sample 1-2 cm of ointment per treatment

To prepare for a blood sample apply the ointment to the intended site of injection (earlobe or digital pulp) approximately 10 minutes beforehand and massage into the skin.

Before taking the blood sample wipe off any residual ointment and disinfect the area of skin. Wearing disposable gloves is recommended. Care should be taken to avoid any ointment being transferred to other areas of skin or other persons.

4.3 Contraindications

– Hypersensitivity to nonylic vanillylamide or β-butoxyethylester of nicotinic acid or to any of the excipients listed in section 6.1; – very sensitive skin; – open wounds; – dermatitis; – diseased skin.

4.4 Special warnings and precautions for use

Due to local skin hyperaemia induced [Invented name] 4 mg/g + 25 mg/g ointment redness, feeling of warmth, itching and burning at the application site are to be expected. These symptoms may be particularly marked if the amount [Invented name] 4 mg/g + 25 mg/g ointment applied is excessive or [Invented name] 4 mg/g + 25 mg/g ointment is intensively rubbed on the skin area. Excessive use or rubbing of [Invented name] 4 mg/g + 25 mg/g ointment may cause blisters of the skin.

Patients have to be informed, that – hands should be thoroughly washed with soap and water immediately after application of [Invented name] 4 mg/g + 25 mg/g ointment, in order to avoid a transferring to unintended skin areas or to other people; – [Invented name] 4 mg/g + 25 mg/g ointment should be applied under no circumstances to the face, eyes or mouth, as this may result in transient face swelling, facial pain, conjunctival irritation, ocular hyperaemia, eye burning, visual disturbance, oral discomfort and stomatitis;

[Invented name] 4 mg/g + 25 mg/g ointment 3 AT/H/0661/001/DC, final SmPC

– [Invented name] 4 mg/g + 25 mg/g ointment should not be used on sensitive skin areas should such as neck, lower abdomen or inside of the thighs; – the skin of people with bright hairs or sensitive people generally can react stronger and therefore the thermal stimulus can be reached even with very low doses of [Invented name] 4 mg/g + 25 mg/g ointment; – before or after applying [Invented name] 4 mg/g + 25 mg/g ointment patients should not take a hot bath or shower, as even hours after application of [Invented name] 4 mg/g + 25 mg/g ointment redness of skin and an intensive feeling of warmth can be induced by sweating or application of warming effects.

[Invented name] 4 mg/g + 25 mg/g ointment contains sorbic acid. Sorbic acid may cause local skin reactions (e.g. contact dermatitis).

Allergens This medicine contains fragrance with α-Isomethyl ionone, α-Amylcinnamaldehyde, α-Amylcinnamyl alcohol, Anisyl alcohol, Evernia furfuracea extract (Treemoss extract), Benzyl alcohol, Benzyl benzoate, Benzyl cinnamate, Benzyl salicylate, Citral, Citronellol, Coumarin, Oakmoss extract, Eugenol, Farnesol, Geraniol, α-Hexylcinnamaldehyde, Hydroxycitronellal, Isoeugenol, Butylphenyl methylpropional (Lilial), Limonene, Linalool, Hydroxyisohexyl 3-Cyclohexene Carboxaldehyde (Lyral), Methyl heptane carbonate, Cinnamaldehyde, Cinnamyl alcohol

The allergens mentioned above may cause allergic reactions.

Benzyl alcohol (included in the list of allergens) Benzyl alcohol may cause allergic reactions and mild local irritation

4.5 Interaction with other medicinal products and other forms of interaction

Interactions with other medicinal products, either locally or systemically administered, are not known.

4.6 Fertility, pregnancy and lactation

Pregnancy and breast-feeding No data are available for [Invented name] 4 mg/g + 25 mg/g ointment regarding administration during pregnancy and lactation. Use of [Invented name] 4 mg/g + 25 mg/g ointment is therefore not recommended during pregnancy and lactation.

Fertility No studies on the effect on human fertility have been conducted.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

The following side effects are based on the post-marketing experience and dataset of 202 clinical trial patients treated with 0.4 % nonivamide and 2.5 % nicoboxil ointment.

Frequency is given according the following convention: Very common: ≥ 1/10 Common: ≥ 1/100 to < 1/10 Uncommon:  1/1,000 to < 1/100

[Invented name] 4 mg/g + 25 mg/g ointment 4 AT/H/0661/001/DC, final SmPC

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: anaphylactic reactions, hypersensitivity reactions

Nervous system disorders Common: skin burning sensation Not known: paraesthesia

Respiratory, thoracic and mediastinal disorders Not known: cough, dyspnoea

Skin and subcutaneous tissue disorders Common: erythema, pruritus Uncommon: rash Not known: application site pustules, localised skin reactions, blister, swelling face, urticaria

General disorders and administration site conditions Common: feeling hot

Reporting of suspected adverse reactions Reporting of 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 in Appendix V.

4.9 Overdose

Symptoms After excessive use of [Invented name] 4 mg/g + 25 mg/g ointment the hyperaemic effects may be aggravated and the severity of the described side effects may increase. Excessive use may especially result in the occurrence of blisters in the affected skin area where [Invented name] 4 mg/g + 25 mg/g ointment was administered. Since nicotinic acid esters show a good percutaneous absorption the overdose of [Invented name] 4 mg/g + 25 mg/g ointment may result in systemic reactions - e.g. redness of the upper part of the body, increase of body temperature, hot flushes, painful hyperaemia and a decrease in blood pressure.

Therapy If too much [Invented name] 4 mg/g + 25 mg/g ointment has been applied, the effect can be reduced by dabbing the skin with a swab soaked in oil (at best ) or enriched in cream. Symptomatic therapy should be applied.

Measures in accidental oral administration: charcoal, liquid paraffin, analgesics, if necessary.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Topical products for joint and muscular pain, and similar agents ATC code: M02AB

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[Invented name] 4 mg/g + 25 mg/g ointment contains two vasodilating active substances, which produce an intensive thermal stimulus on the skin for many hours.

Nonyl vanillylamide (Nonivamide) Nonyl vanillylamide is a synthetic capsaicin-analogue with analgesic properties, which are assumed to result from depletion of in the peripheral nociceptive C-fibres and A-delta-nerve-fibres upon repetitive application on the skin. By stimulating the afferent nerve endings in the skin, nonylic vanillylamide has a dilatory effect on the surrounding blood vessels accompanied by an intense, long- lasting feeling of warmth.

β-butoxyethylester of nicotinic acid (Nicoboxil) Nicotinic acid is a B-vitamin which has vasodilatory properties mediated by prostaglandin. The hyperaemic effect of β-butoxyethylester of nicotinic acid has an earlier onset and it is more intense than the nonivamide hyperaemic effect.

Combination Nonylic vanillylamide and β-butoxyethylester of nicotinic acid both have complementary vasodilatory properties reducing the time to hyperaemic skin reaction upon application.

This leads to a local increase of the circulation of the skin. By this [Invented name] 4 mg/g + 25 mg/g ointment produces a sustainable feeling of warmth.

Topical administration of the nonivamide/nicoboxil increased the concentration of oxygenated haemoglobin and tissue oxygen saturation significantly towards arterial levels in skin as well as the concentration of oxygenated haemoglobin in muscle of the treated legs already after 15 minutes, with stronger and faster effects in skin. The topical application of nonivamide/nicoboxil increased blood flow in smaller vessels of skin and muscle tissue.

5.2 Pharmacokinetic properties

[Invented name] 4 mg/g + 25 mg/g ointment is applied topically and clinical effect occurs at the application site. Therefore no systemic pharmacokinetic data are available.

The reaction (erythema and increased skin temperature) occurs a few minutes after application, rapid penetration of the active principles is obvious.

5.3 Preclinical safety data

Single dermal application of a large amount of 0.4 % nonivamide and 2.5 % nicoboxil ointment caused an immediate pain reaction, accompanied by lethargy, mild dyspnoea and diarrhoea. Instillation into the eye was associated with transient irritation in the eyes. The repeated dermal application of high doses of 0.4 % nonivamide and 2.5 % nicoboxil ointment (up to 5 g/kg body weight over 15 days) only caused skin irritations, which resolved completely on discontinuation of treatment. There were no significant systemic changes in terms of haematology, urinalysis, pathological and histopathological examination.

There are no reports available for reproduction toxicity, genotoxicity or carcinogenicity.

6. PHARMAZEUTICAL PARTICULARS

6.1 List of excipients

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Sorbic acid, citronella oil, diisopropyl adipate, silica colloidal anhydrous, paraffin white soft, water purified

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

Can be used for 6 months after first opening.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Aluminium tube of 20 g

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8. MARKETING AUTHORISATION NUMBER

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORIZATION

Date of first authorisation: {DD month YYYY}>

<[To be completed nationally]>

10. DATE OF REVISION OF THE TEXT

MM/YYYY <[To be completed nationally]>

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