Sheep

Immediately following subcutaneous injection, activity suggesting pain, sometimes intense but usually transient, has been observed in some sheep.

Pigs

Mild and transient pain reactions may be seen in some pigs following subcutaneous injection.

All these reactions disappeared without treatment.

4.7

Use during pregnancy, lactation or lay

PANOMEC Injection for Cattle, Sheep and Pigs can be administered to

cows and ewes at any stage of pregnancy or lactation provided that the

milk is not intended for human consumption, and to sows at any stage of

pregnancy or lactation. It can be used in breeding ewes, rams, sows and

boars and will not affect fertility. PANOMEC Injection for Cattle, Sheep

and Pigs can be given to all ages of animals including young calves,

lambs and piglets.

Please also refer to point 4.4.

4.8

Interaction with other medicinal products and other forms of interaction

PANOMEC Injection for Cattle, Sheep and Pigs has been used

concurrently without adverse effects with foot and mouth disease vaccine

or clostridial vaccine, given at separate injection sites.

Adequate vaccination of sheep against clostridial infections is strongly recommended.

4.9

Amounts to be administered and administration route

PANOMEC Injection for Cattle, Sheep and Pigs should be given only by

subcutaneous injection at the recommended dosage level of 200 mcg

ivermectin per kg bodyweight under the loose skin in front of, or behind,

the shoulder in cattle and in the neck in sheep. At the recommended

dosage level of 300 mcg ivermectin per kg of bodyweight, PANOMEC

Injection for Cattle, Sheep and Pigs should be given only subcutaneously

in the neck in pigs.

Syringes must be filled from the vial through a dry sterile draw-off

needle that has been placed in the vial stopper. Vial stoppers must not

be broached more than 20 times.

This product does not contain an antimicrobial preservative. Swab septum before removing each dose.

Use sterile needle and syringe. When treating groups of animals use only an automatic dosing device (with vented draw-off apparatus when using the 50ml vial).

To ensure administration of a correct dose, body weight should be determined as accurately as possible; accuracy of the dosing device should be checked.

Use this chart as a guide in working out the appropriate dose rate:

Cattle (1ml/50kg)

Sheep (0.5ml/25kg)

Pigs (1ml/33kg)

Bodyweight (kg)

Dose Volume (ml)

Bodyweight (kg)

Dose Volume (ml)

Bodyweight (kg)

Dose Volume (ml)

Up to 50

51 – 100

101 – 150

151 – 200

201 – 250

251 – 300

301 – 350

351 - 400

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

Up to 5

5.1 – 10

10.1 – 15

15.1 – 25

25.1 – 50

50.1 – 75

75.1 - 100

0.1

0.2

0.3

0.5

1.0

1.5

2.0

Less than 4

5 – 7

8 – 10

11 – 13

14 – 16

17 – 33

34 – 50

51 – 66

67 – 99

100 – 133

134 – 166

167 - 200

0.1

0.2

0.3

0.4

0.5

1.0

1.5

2.0

3.0

4.0

5.0

6.0

For cattle weighing over 400kg calculate the dose at the rate of 1ml per 50kg bodyweight.

For sheep weighing over 100kg calculate the dose at the rate of 0.5ml per 25kg bodyweight.

For pigs weighing over 200kg calculate the dose at the rate of 1ml per 33kg bodyweight.

When treating pigs and sheep of less than 16kg, seek veterinary advice regarding the use of 1ml disposable syringes graduated in increments of 0.1ml. When treating individual sheep, a syringe, not exceeding 2ml and calibrated in increments of 0.1 ml, should be used.

Each ml contains 10 mg of ivermectin sufficient to treat 50 kg of bodyweight of cattle and sheep and 33 kg of bodyweight of pigs. The injection may be given with any standard automatic or single-dose or hypodermic syringe. Use of 17 gauge x 1/2 inch needle is suggested.

Replace with a fresh sterile needle after every 10 to 12 animals. Injection of wet or dirty animals is not recommended.

For the treatment and control of sheep scab (Psoroptes ovis), two injections with a seven-day interval are required to treat clinical signs of scab and to eliminate mites.

4.10

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

Cattle

Single doses of 4.0 mg ivermectin per kg (20 x the use level) given subcutaneously resulted in ataxia and depression.

Sheep

At oral dose levels up to 4 mg ivermectin per kg (20 x the use level)

given subcutaneously resulted in ataxia and depression.

Pigs

A dose of 30 mg ivermectin per kg (100 x the recommended dose of 0.3

mg per kg) injected subcutaneously to pigs caused lethargy, ataxia,

bilateral mydriasis, intermittent tremors, laboured breathing and lateral recumbency.

No antidote has been identified; however, symptomatic therapy may be

beneficial.

4.11

Withdrawal periods

Cattle ( meat & Offal ) : 49 days

Cattle ( milk ) : Do not use in cattle producing milk for human consumption.

Do not use in non-lactating dairy cows, including pregnant heifers, within 60 days of calving.

Sheep ( meat & offal ) : 37 days

Sheep ( milk ) : Do not use in sheep producing milk for human consumption

Pigs ( meat & offal ) : 19 days.

5.

PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group:

Endectocides, macrocyclic lactones, avermectins

ATCVet code: QP54AA01

5.1

Pharmacodynamic properties

Mechanism of Action

Ivermectin is a member of the macrocyclic lactone class of endectocides which have a unique mode of action. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite. Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA).

The margin of safety for compounds of this class is attributable to the fact that mammals do not have glutamate-gated chloride channels, the macrocyclic lactones have a low affinity for other mammalian ligand-gated chloride channels and they do not readily cross the blood-brain barrier.

5.2

Pharmacokinetic properties

Maximum plasma concentration

Cattle

At a dose level of 0.2 mg ivermectin per kg a maximum plasma

concentration of 35-50 ng/ml is reached in +/- 2 days and the half-life

in plasma is 2.8 days. It is also established that ivermectin is carried

mainly in the plasma (80%). This distribution between plasma and blood

cells remain relatively constant.

Sheep

At a dose level of 0.3 mg ivermectin per kg an average peak of 16 ng/ml is reached one day after injection.

Pigs

During trials carried out at a dose rate of 0.2 mg/kg ivermectin, a

plasma concentration of 10-20 ng/ml was reached in +/- 2 days and

half-life in plasma was 0.5 day.

Excretion: length of time and route

Cattle

A liquid chromatographic method with fluorescence detection allows the

determination of ivermectin residues in tissues. After an injection of 0.3

mg ivermectin per kg, the liver (target tissue) had residues ranging from

454 ppb at 2 days post treatment to 11 ppb at 28 days post treatment.

The injection site had residues shortly after treatment, ranging up to 69

ppm at 2 days withdrawal, but by 28 days the average residue was

negligible ( < 2 ppb). Cattle receiving a single dose of tritium-labelled

ivermectin (0.2 - 0.3 mg/kg body weight) were slaughtered at 7, 14, 21

and 28 days after dosing. Composites of faeces collected during the first 7 days after dosing contained almost all the dosed radioactivity. Only

about 1-2 % of the dosed radioactivity was excreted in the urine.

Analyses of the faeces showed that about 40-50% of the excreted radioactivity was present as unaltered drug. The remaining 50-60% was present as metabolites or degradation products almost all which were more polar than the ivermectin.

Sheep

A liquid chromatographic method with fluorescence detection allows the determination of ivermectin residues in tissues. After an injection of 0.3 mg ivermectin per kg, the liver (target tissue) had residues ranging from 160 ppb at 3 days post treatment to 7.2 ppb at 28 days post treatment. The highest residue levels were recovered in fat (from 230 ppb at 3 days post treatment to 13 ppb at 28 days post treatment). Residues in all tissues were below 30 ppb at 28 days post treatment. Radioactive ivermectin was administered to sheep at a dose rate of 0.3 mg per kg. Analyses of the faeces showed that about 99% of the drug and its metabolites are excreted in the faeces, +/- 1 % being excreted in the urine.

Pigs

A liquid chromatographic method with fluorescence detection allows the

determination of ivermectin residues in tissues. After an injection of 0.4

mg/kg ivermectin the liver (target tissue) contained average residues

ranging from 69 ppb at 3 days post dose to 13 ppb at 14 days post

dose. No liver residue (< 2 ppb) was found at 28 days post dose.

Swine receiving a single dose of tritium-labelled ivermectin (0.3-0.4 mg/kg) were slaughtered at 1, 7, 14 and 28 days after dosing. Composites of faeces collected during the first 7 days after dosing contained only about 36% of the dosed radioactivity. Less than 1% of the dosed radioactivity was found in the

urine. Analysis of the faeces showed that about 40% of the excreted radioactivity was unaltered drug.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Glycerol Formal

Propylene Glycol

6.2

Incompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products

6.3

Shelf-life,

Shelf-life of the veterinary medicinal product as packaged for sale: 5 years.

Shelf-life after first opening the immediate packaging: 6 months.

6.4

Special precautions for storage

Protect from direct sunlight and store below 30°C.

Keep out of reach of children.

This product does not contain any antimicrobial preservative.

Following withdrawal of the first dose, use the product within 6 months.

Discard unused material.

6.5

Nature and composition of immediate packaging

Multiple-dose rubber-capped polyethylene bottles of 50 ml, 200 ml and 500 ml containing a sterile non-aqueous solution for parenteral administration. Bottles are stoppered and then either sealed by heat or crimp-sealed with an aluminium cap.

6.6

Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products, if appropriate

EXTREMELY DANGEROUS TO FISH AND AQUATIC LIFE. Do not

contaminate ponds, waterways or ditches with product or empty container.

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

Merial Animal Health Limited

PO Box 327

Sandringham House

Harlow Business Park

Harlow

Essex

CM19 5TG

8.

MARKETING AUTHORISATION NUMBER

Vm 08327/4193

9.

DATE OF FIRST AUTHORISATION

6 April 1995

10.

DATE OF REVISION OF THE TEXT

September 2016

11.

ANY OTHER INFORMATION REQUIRED BY THE SECRETARY OF STATE

Not applicable.