VarroMed (oxalic acid dihydrate / formic acid) – Summary of product characteristics - QP53AG

1.NAME OF THE VETERINARY MEDICINAL PRODUCT

VarroMed 5 mg/ml + 44 mg/ml bee-hive dispersion for honey bees

2.QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substances:
Each ml contains:
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 PARTICULARS

4.1Target species

Honey bees

4.2Indications for use, specifying the target species

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

4.3Contraindications

Do not use during nectar flow.

4.4Special warnings for each target species

VarroMed should only be used as part of an integrated Varroa control programme. Efficacy was only investigated in hives with low to moderate mite infestation rates.

4.5Special 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 VarroMed 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.

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. 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.

−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.

−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.

4.6Adverse 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 displaying adverse reaction(s) during the course of one treatment)

-common (more than 1 but less than 10 colonies in 100 colonies)

-uncommon (more than 1 but less than 10 colonies in 1,000 colonies)

-rare (more than 1 but less than 10 colonies in 10,000 colonies)

-very rare (less than 1 colonies in 10,000 colonies, including isolated reports.

4.7Use during pregnancy, lactation or lay

Not applicable.

4.8Interaction 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.

		up to 5x	possible in late	administrations).
			summer/early autumn with
			decreasing colony	The treatment should be repeated
			population, and when the	twice more (that is to a maximum
			natural mite fall is more	of 5 treatments), if more than 150
			than 4 mites per day.
				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		Treatment should be	Not applicable
		1x	conducted at the start of the
	(broodless)		broodless period in hives	(single treatment only).
			with Varroa infestation

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 VarroMed evenly over the bees, particular in the winter cluster.

VarroMed should not be used during the nectar flow, or when honey chambers are attached to the hive.

Before use, the product should be 25 to 35 °C warm, 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.

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

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 VarroMed 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 VarroMed 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.

5.2Pharmacokinetic particulars

The pharmacokinetics of VarroMed 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 PARTICULARS

6.1List of excipients

Caramel colour (E150d)

Sucrose syrup

Propolis tincture 20%

Star anise oil

Lemon oil

Citric acid monohydrate

Purified water

6.2Incompatibilities

Do not mix with any other veterinary medicinal product.

6.3Shelf 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.

6.5Nature 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

5164 Seeham

AUSTRIA

8.MARKETING AUTHORISATION NUMBER(S)

9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10 DATE OF REVISION OF THE TEXT

DD month YYYY

Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/.

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

VarroMed 75 mg + 660 mg bee-hive dispersion for honey bees

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substances:

Each single dose sachet contains:

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 PARTICULARS

4.1 Target species

Honey bees

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

VarroMed should only be used as part of an integrated Varroa control programme. 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 VarroMed 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.

			decreasing colony	administrations).
			population, and when the
			natural mite fall is more	The treatment should be repeated
			than 4 mites per day.	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		Treatment should be	Not applicable
		1x	conducted at the start of the
	(broodless)		broodless period in hives	(single treatment only).
			with Varroa infestation

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 VarroMed evenly over the bees, particular in the winter cluster.

VarroMed should not be used during the nectar flow, or when honey chambers are attached to the hive.

Before use, the product should be 25 to 35 °C warm, 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.

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

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 VarroMed 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 VarroMed 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 VarroMed 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 PARTICULARS

6.1 List of excipients

Caramel colour (E150d)

Sucrose syrup

Propolis tincture 20%

Star anise oil

Lemon oil

Citric acid monohydrate

Purified water

6.2 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

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

5164 Seeham

AUSTRIA

8. MARKETING AUTHORISATION NUMBER(S)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10 DATE OF REVISION OF THE TEXT

DD month YYYY

Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/.

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.