VarroMed - summary of medicine characteristics

SUMMARY OF PRODUCT CHARACTERISTICS

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substances:

Formic acid                     5 mg

Oxalic acid dihydrate            44 mg (equivalent to 31.42 mg oxalic acid anhydrous)

Excipients:

Caramel colour (E150d)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Bee-hive dispersion.

Slightly brown to dark brown aqueous dispersion.

4. CLINICAL PARTICULARS4.1 Target species

Honey bees (Apis mellifera ).

• 4.2 Indications for use, specifying the target species

Treatment of varroosis (Varroa destructor ) in honey bee colonies with and without brood.

4.3 Contraindications

Do not use during nectar flow.

• 4.4 Special warnings for each target species

This veterinary medical product should only be used as part of an integrated Varroa control programme. Mite levels should be monitored regularly.

Efficacy was only investigated in hives with low to moderate mite infestation rates.

• 4.5 Special precautions for use

Special precautions for use in animals

Following treatment, worker bees with a protruding proboscis were found. This might be associated with insufficient access to drinking water. Ensure, therefore, that treated bees have sufficient access to drinking water.

The long-term tolerance of the veterinary medicinal product has only been tested over 18 months, i.e. a negative impact of the product on queens or colony development after longer treatment periods cannot be excluded. It is advised to check regularly that the queen is present, but avoid disturbing the hives in the days following treatment.

All colonies placed at the same location should be treated at the same time to minimize the risk of reinfestation.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

• - This veterinary medicinal product is irritating to the skin and eyes. Avoid contact with the skin,

eyes and mucous membranes. Personal protective equipment consisting of protective clothing, acid-resistant gloves and glasses should be worn when handling the veterinary medicinal product. Change heavily contaminated clothes as soon as possible and wash before re-use. In case of accidental spillage onto skin, wash the affected areas immediately with running water. In case of accidental spillage into the eye(s), flush the eye(s) immediately with clear running water for 10 minutes.

• - Children should not come into contact with this veterinary medicinal product. Accidental ingestion may cause adverse reactions.

• - People with known sensitivity to formic acid or oxalic acid should administer the veterinary medicinal product with caution.

• - Do not eat, drink or smoke while using the product.

• 4.6 Adverse reactions (frequency and seriousness)

Increased mortality in worker bees was very commonly observed in the clinical and preclinical trials following treatment with VarroMed. This effect is considered to be associated with the oxalic acid in VarroMed, and increased with increasing doses and/or repeated treatments.

The frequency of adverse reactions is defined using the following convention:

• – very common (more than 1 in 10 colonies treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 colonies in 100 colonies treated)

• – uncommon (more than 1 but less than 10 colonies in 1,000 colonies treated)

• – rare (more than 1 but less than 10 colonies in 10,000 colonies treated)

• – very rare (less than 1 colony in 10,000 colonies treated, including isolated reports).

• 4.7 Use during pregnancy, lactation or lay

Not applicable.

4.8 Interaction with other medicinal products and other forms of interaction

None known.

The concomitant use of other acaricidal products should be avoided because increased toxicity to bees might occur.

• 4.9 Amounts to be administered and administration route

In-hive use.

To be trickled onto bees in occupied bee-spaces of the brood chamber.

Dose :

Shake well before use.

The dose should carefully be adjusted to the colony size (see dosing table). Determine the colony size and number of occupied bee spaces to be treated, and select the correct amount of product required. The following dosing scheme applies:

No. of bees	5,000 – 7,000	7,000 – 12,000	12,000 – 30,000	> 30,000
VarroMed (ml)	15 ml	15 to 30 ml	30 to 45 ml	45 ml

The use of the veterinary medicinal product with the above dosing scheme only applies for hives with vertical frames that can be accessed from the top, as the treatment of bees in other types of hives has not been investigated.

The multi-dose container has a graduated dosing scale for accurate dosing.

Frequency of treatment:

Repeated administration of the veterinary medicinal product might be required for spring or autumn treatment at intervals of 6 days, repeated applications should only be performed as indicated by mitefall in accordance with the following table:

Season	No. of applications	Threshold for first treatment	Repeated Treatment:
Spring	1× or 3×	Treatment should be conducted at the start of the season with increasing colony population and when the natural mite fall is more than 1 mite per day	The treatment should be repeated twice more (that is to a maximum of 3 treatments), if more than 10 mites are detected on the floorboard within 6 days after the first treatment (maximum of 3 treatments).
Autumn	3×	Treatment should be conducted as soon as	The treatment should be repeated twice, 6 days apart (i.e.

	up to 5×	possible in late summer/early autumn with decreasing colony population, and when the natural mite fall is more than 4 mites per day.	3 administrations). The treatment should be repeated twice more (that is to a maximum of 5 treatments), if more than 150 mites (colonies from the second year) or more than 90 mites (nucleus colonies in the first year) are detected on the floorboard within 6 days after the third administration.
Winter (broodless)	1×	Treatment should be conducted at the start of the broodless period in hives with Varroa infestation	Not applicable (single treatment only).

Advice on correct administration

Timing of administration: the product should be used primarily at times when bees have low flight activity (late afternoon, evening). Darkness facilitates distribution of the product between the bees. To avoid overdoses to individual bees, care should be taken to administer the veterinary medical product evenly over the bees, particular in the winter cluster.

The veterinary medicinal product should not be used during the nectar flow, or when honey chambers are attached to the hive.

Before use, the product should be warmed up to the temperature from 25 to 35 °C and then shaken well.

It is recommended to remove the wax bridges between the top bars of the frames before administration of the product.

Do not lift the frames during administration and for approximately one week after the last treatment.

In order to establish the Varroa infestation level in a hive, the mite mortality must be monitored: mite fall should be recorded on the hive floorboard before the first treatment, and up to 6 days after each treatment.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

Following the administration of a 10% solution of oxalic acid dihydrate in 50% sugar solution, permanent lesions in digestive and excretory organs were noted after 72 hours (h).

Oxalic acid concentrations of 20% in a 50% sugar solution led to acute bee mortalities of more than 60%.

In case of accidental overdose (e.g. spillage of a large quantity of the veterinary medicinal product into a hive) the best counter measure includes exchanging the hive body and cleaning the frames with water from all visible spills of the dispersion.

• 4.11 Withdrawal period(s)

Honey: Zero days.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Ectoparasiticides for topical use, including insecticides, organic acids, combinations.

ATCvet code: QP53AG30.

5.1 Pharmacodynamic properties

Formic acid probably kills Varroa mites by inhibiting electron transport in their mitochondria through the binding of cytochrome c oxidase, thereby inhibiting energy metabolism and may produce a neuro-excitatory effect on arthropod neurons after evaporation in the hive air (at least 500 ppm). No data are available which confirm this activity after trickling of 0.5% formic acid; however, formic acid in the fixed combination of the veterinary medicinal product is considered to extend the duration of the effect of oxalic acid, and to improve the tolerance of the product.

The mode of action of oxalic acid against Varroa mites is unknown, but direct contact between the mites and oxalic acid is required. It is assumed that oxalic acid acts via direct contact or by ingestion of oxalic haemolymph. The acaricidal effect may be due mainly to the low pH of the formulation. Oxalic acid treatments administered in water are ineffective, but administration in sugar water improves efficacy by increasing its adhesion to the bees.

• 5.2 Pharmacoki­netic particulars

The pharmacokinetics of the veterinary medicinal product have not been studied.

However, literature data show that oxalic acid is absorbed to a limited extent after topical application at therapeutic doses under normal beekeeping conditions. Data have also shown that oxalic acid can be orally ingested by bees due to increased self-grooming after dermal application, which might lead to increased toxicity.

The pharmacokinetics of formic acid in bees is not known.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Caramel colour (E150d)

Sucrose syrup

Propolis tincture 20%

Star anise oil

Lemon oil

Citric acid monohydrate

Purified water

6.2 Major incompatibilities

Do not mix with any other veterinary medicinal product.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

Shelf life after first opening the immediate packaging: 30 days.

6.4. Special precautions for storage

Do not store above 25 °C.

Keep the bottle tightly closed.

Keep the bottle in the outer carton in order to protect from light.

• 6.5 Nature and composition of immediate packaging

Cardboard box containing an HDPE bottle with dropper nozzle (LDPE) and screw cap (with tamper evident seal). The bottle has a graduated dosing scale.

Box containing 1 bottle of 555 ml dispersion.

• 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

BeeVital GmbH

Wiesenbergstraße 19

A-5164 Seeham

AUSTRIA

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/16/203/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 02/02/2017

Date of the last renewal:

10. DATE OF REVISION OF THE TEXT

Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency ( ).

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each single dose sachet contains:

Active substances:

Formic acid                 75 mg

Oxalic acid dihydrate         660 mg (equivalent to 471.31 mg oxalic acid anhydrous)

Excipients:

Caramel colour (E150d)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Bee-hive dispersion.

Slightly brown to dark brown aqueous dispersion.

4. CLINICAL PARTICULARS4.1 Target species

Honey bees (Apis mellifera ).

• 4.2 Indications for use, specifying the target species

Treatment of varroosis (Varroa destructor ) in honey bee colonies with and without brood.

4.3 Contraindications

Do not use during nectar flow.

• 4.4 Special warnings for each target species

This veterinary medicinal product should only be used as part of an integrated Varroa control programme. Mite levels should be monitored regularly.

Efficacy was only investigated in hives with low to moderate mite infestation rates.

• 4.5 Special precautions for use

Special precautions for use in animals

Following treatment, worker bees with a protruding proboscis were found. This might be associated with insufficient access to drinking water. Ensure, therefore, that treated bees have sufficient access to drinking water.

The long-term tolerance of the veterinary medicinal product has only been tested over 18 months, i.e. a negative impact of the product on queens or colony development after longer treatment periods cannot be excluded. It is advised to check regularly that the queen is present, but avoid disturbing the hives in the days following treatment.

All colonies placed at the same location should be treated at the same time to minimize the risk of reinfestation.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

• - This veterinary medicinal product is irritating to the skin and eyes. Avoid contact with the skin, eyes and mucous membranes. Personal protective equipment consisting of protective clothing, acid-resistant gloves and glasses should be worn when handling the veterinary medicinal product. Change heavily contaminated clothes as soon as possible and wash before re-use. In case of accidental spillage onto skin, wash the affected areas immediately with running water. In case of accidental spillage into the eye(s), flush the eye(s) immediately with clear running water for 10 minutes.

• - Children should not come into contact with this veterinary medicinal product. Accidental ingestion may cause adverse reactions.

• - People with known sensitivity to formic acid or oxalic acid should administer the veterinary medicinal product with caution.

• - Do not eat, drink or smoke while using the product.

• 4.6 Adverse reactions (frequency and seriousness)

Increased mortality in worker bees was very commonly observed in the clinical and preclinical trials following treatment with VarroMed. This effect is considered to be associated with the oxalic acid in VarroMed, and increased with increasing doses and/or repeated treatments.

The frequency of adverse reactions is defined using the following convention:

• – very common (more than 1 in 10 colonies treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 colonies in 100 colonies treated)

• – uncommon (more than 1 but less than 10 colonies in 1,000 colonies treated)

• – rare (more than 1 but less than 10 colonies in 10,000 colonies treated)

• – very rare (less than 1 colony in 10,000 colonies treated, including isolated reports).

• 4.7 Use during pregnancy, lactation or lay

Not applicable.

4.8 Interaction with other medicinal products and other forms of interaction

None known.

The concomitant use of other acaricidal products should be avoided because increased toxicity to bees might occur.

• 4.9 Amounts to be administered and administration route

In-hive use.

To be trickled onto bees in occupied bee-spaces of the brood chamber.

Dose :

Shake well before use.

The dose should carefully be adjusted to the colony size (see dosing table). Determine the colony size and number of occupied bee spaces to be treated, and select the correct amount of product required. The following dosing scheme applies:

No. of bees	5,000 – 7,000	7,000 – 12,000	12,000 – 30,000	> 30,000
VarroMed (ml)	15 ml	15 to 30 ml	30 to 45 ml	45 ml

The use of the veterinary medicinal product with the above dosing scheme only applies for hives with vertical frames that can be accessed from the top, as the treatment of bees in other types of hives has not been investigated.

Frequency of treatment:

Repeated administration of the veterinary medicinal product might be required for spring or autumn treatment at intervals of 6 days, repeated applications should only be performed as indicated by mitefall in accordance with the following table:

Season	No. of applications	Threshold for first treatment	Repeated Treatment:
Spring	1× or 3×	Treatment should be conducted at the start of the season with increasing colony population and when the natural mite fall is more than 1 mite per day	The treatment should be repeated twice more (that is to a maximum of 3 treatments), if more than 10 mites are detected on the floorboard within 6 days after the first treatment (maximum of 3 treatments).
Autumn	3× up to 5×	Treatment should be conducted as soon as possible in late summer/early autumn with	The treatment should be repeated twice, 6 days apart (i.e. 3 administrations).

		decreasing colony population, and when the natural mite fall is more than 4 mites per day.	The treatment should be repeated twice more (that is to a maximum of 5 treatments), if more than 150 mites (colonies from the second year) or more than 90 mites (nucleus colonies in the first year) are detected on the floorboard within 6 days after the third administration.
Winter (broodless)	1×	Treatment should be conducted at the start of the broodless period in hives with Varroa infestation	Not applicable (single treatment only).

Advice on correct administration

Timing of administration: the product should be used primarily at times when bees have low flight activity (late afternoon, evening). Darkness facilitates distribution of the product between the bees. To avoid overdoses to individual bees, care should be taken to administer the veterinary medicinal product evenly over the bees, particular in the winter cluster.

The veterinary medicinal product should not be used during the nectar flow, or when honey chambers are attached to the hive.

Before use, the product should be warmed up to the temperature from 25 to 35 °C and then shaken well.

It is recommended to remove the wax bridges between the top bars of the frames before administration of the product.

Do not lift the frames during administration and for approximately one week after the last treatment.

In order to establish the Varroa infestation level in a hive, the mite mortality must be monitored: mite fall should be recorded on the hive floorboard before the first treatment, and up to 6 days after each treatment.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

Following the administration of a 10% solution of oxalic acid dihydrate in 50% sugar solution, permanent lesions in digestive and excretory organs were noted after 72 hours (h).

Oxalic acid concentrations of 20% in a 50% sugar solution led to acute bee mortalities of more than 60%.

In case of accidental overdose (e.g. spillage of a large quantity of veterinary medicinal product into a hive) the best counter measure includes exchanging the hive body and cleaning the frames with water from all visible spills of the dispersion.

• 4.11 Withdrawal period(s)

Honey: Zero days.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Ectoparasiticides for topical use, including insecticides, organic acids, combinations

ATCvet code: QP53AG30.

5.1 Pharmacodynamic properties

Formic acid probably kills Varroa mites by inhibiting electron transport in their mitochondria through the binding of cytochrome c oxidase, thereby inhibiting energy metabolism and may produce a neuro-excitatory effect on arthropod neurons after evaporation in the hive air (at least 500 ppm). No data are available which confirm this activity after trickling of 0.5% formic acid; however, formic acid in the fixed combination of the veterinary medicinal product is considered to extend the duration of the effect of oxalic acid, and to improve the tolerance of the product.

The mode of action of oxalic acid against Varroa mites is unknown, but direct contact between the mites and oxalic acid is required. It is assumed that oxalic acid acts via direct contact or by ingestion of oxalic haemolymph. The acaricidal effect may be due mainly to the low pH of the formulation. Oxalic acid treatments administered in water are ineffective, but administration in sugar water improves efficacy by increasing its adhesion to the bees.

• 5.2 Pharmacoki­netic particulars

The pharmacokinetics of the veterinary medicinal product have not been studied.

However, literature data show that oxalic acid is absorbed to a limited extent after topical application at therapeutic doses under normal beekeeping conditions. Data have also shown that oxalic acid can be orally ingested by bees due to increased self-grooming after dermal application, which might lead to increased toxicity.

The pharmacokinetics of formic acid in bees is not known.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Caramel colour (E150d)

Sucrose syrup

Propolis tincture 20%

Star anise oil

Lemon oil

Citric acid monohydrate

Purified water

6.2 Major incompatibilities

Do not mix with any other veterinary medicinal product.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

Shelf life after first opening the immediate packaging: use immediately.

6.4. Special precautions for storage

Do not store above 25 °C.

Keep the sachets in the outer carton in order to protect from light. Opened sachets should not be stored.

• 6.5 Nature and composition of immediate packaging

Cardboard box containing 12 single-dose sachets (foil PETP/ Al /LDPE), each containing 15 ml dispersion. Sachets are perforated for opening.

• 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

7. MARKETING AUTHORISATION HOLDER

BeeVital GmbH

Wiesenbergstraße 19

A-5164 Seeham

AUSTRIA

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/16/203/002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 02/02/2017

Date of the last renewal: