Vetbromide 600 mg Tablets for Dogs

Composition

Each tablet contains:

Active substances:

Potassium bromide …………….. 600 mg

Excipients:

Qualitative composition of excipients and other constituents

Lactose monohydrate

Cellulose, microcrystalline

Silica, colloidal anhydrous

Glycerol dibehenate

Magnesium stearate

Round, white tablet with 2 scored lines on each side. Tablets can be divided into 2 or 4 equal parts.

3

Pharmacological properties

4.1 ATCvet code: QN03AX91

4.2 Pharmacodynamics

Potassium bromide is a halide anticonvulsant. Bromide replaces chloride in all body fluids. It competes with chloride transport across nerve cell membranes and inhibits sodium transport and so causes membrane hyperpolarisation. This hyperpolarisation raises the seizure threshold and prevents the spread of epileptic discharges. Bromide has effects on active transport across ganglial cell membranes and affects passive movements of ions by competition with chloride for anion channels in post-synaptic membranes that are activated by inhibitory neurotransmitters. This potentiates the effect of GABA which results in a synergistic activity of bromide with other drugs that have GABA-ergic activity, such as phenobarbital.

4.3 Pharmacokinetics

After oral administration, the potassium bromide salt dissociates and bromide ions are absorbed passively by the gastrointestinal tract. After absorption, the bromide ion rapidly and widely distributes, as does chloride, throughout the extra-cellular space and into cells. As the bromide level is increased in the body, the concentration of chloride is decreased in direct proportion to the increase in bromide.

The half-life can vary significantly with dietary chloride content, from approximately 14 days to more than 40 days. Due to this extremely long half-life, it can take several weeks / months to achieve steady state serum concentrations.

Bromide ions are excreted unchanged as the monovalent anion. Excretion of bromide is mainly via glomerular filtrations in the kidneys. The rate of elimination of bromide ions increases with chloride intake, as bromide competes with chloride for tubular reabsorption.

3

Target species

Dogs

3

Indications

An antiepileptic agent for use in the control of idiopathic epileptic seizures, either as a single agent or as an adjunct to phenobarbital in the control of refractory cases of idiopathic epilepsy.

3

Dosage

Oral use.

Administer twice daily with food in order to reduce the risk of gastrointestinal irritation.

In dogs with severe and frequent seizures or when a dog is being switched rapidly from phenobarbital to potassium bromide, a loading dose of 60 mg/kg bodyweight twice daily, for 5 days (equivalent to a total daily dose of 120 mg/kg) can be administered in order to quickly reach therapeutic serum concentrations.

The maintenance dose should be titrated to the individual dog as the required dosage and therapeutic serum bromide concentration may vary between animals and depends on the nature and severity of the underlying disease.

Monotherapy:

The recommended starting dose is 30 mg/kg bodyweight twice daily (equivalent to a total daily dose of 60 mg/kg).

Adjunctive treatment, in combination with phenobarbital:

The recommended starting dose is 15 mg/kg bodyweight twice daily (equivalent to a total daily dose of 30 mg/kg). Use in dogs with a bodyweight of less than 10 kg should be subject to a risk/benefit assessment, see section 3.5.

At the beginning of treatment, bromide serum concentrations should be checked regularly, e.g. 1 week and 1 month after the loading period and three months after treatment initiation at maintenance dosage. Therapeutic serum levels vary between 1000 mg/L to 3000 mg/L when potassium bromide is used as monotherapy and between 800 mg/L and 2000 mg/L, when used as adjunctive treatment. Close monitoring for side effects is advisable, particularly when serum bromide concentrations have reached the upper limit of the therapeutic range for monotherapy.

It is recommended to administer at least half of the initial starting dose to dogs with mild or moderate renal insufficiency, with more frequent monitoring of serum bromide levels (see section 3.5).

If the clinical response is not satisfactory or if adverse reactions occur, the dose may be adjusted based on the dog’s serum bromide levels. Serum concentrations should be measured after each dose adjustment once steady state serum levels have been reached (typically 3 months after a change), unless earlier evaluation is necessary. Long term monitoring of serum bromide concentrations should be performed as clinically justified by the individual case.

3

Contraindications

Do not use in dogs with severe renal insufficiency.

Do not use in cases of hypersensitivity to the active substances or to any of the excipients.

3

Adverse reactions

Dogs:

1 These adverse reactions may disappear after the first stage of treatment but may also persist in dogs on higher doses of therapy. In these cases, symptoms usually disappear following a reduction in dose. If the dog appears too sedated, assess the serum concentrations of bromide and, if applicable, phenobarbital to determine whether the dose of either should be reduced.

If potassium bromide dose is reduced, serum bromide concentrations should be monitored in order to ensure that they fall within the therapeutic range.

2 Although pancreatitis has been suggested to occur in association with the administration of bromide and/or phenobarbital, there is no conclusive evidence of a direct causal relationship between bromide administration and the development of pancreatitis in dogs.

3 Treating dogs with potassium bromide can cause a decrease in T4 plasma concentration, although this is not necessarily clinically relevant.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See the package leaflet for respective contact details.

3

Warnings

Special precautions for safe use in the target species:

Do not abruptly discontinue therapy as this may precipitate seizures.

This veterinary medicinal product should be used with caution in dogs with mild or moderate renal insufficiency, since excretion of bromide is reduced (see also section 3.3). To prevent bromide accumulation and a relative overdose of bromide (see 3.10), administer a reduced dose and monitor the serum bromide concentration closely (see 3.9).

A reduction in chloride intake (low sodium diet) can increase the likelihood of adverse reactions or bromide intoxication (see section 3.8 and 3.10).

Close monitoring for adverse reactions is advisable at higher serum bromide concentrations.

Administration on an empty stomach may induce vomiting.

Dogs weighing less than 10 kg cannot be accurately dosed with the recommended starting dose for adjunctive treatment of 15 mg/kg twice daily, as the minimum dose achievable by division of the veterinary medicinal product is 150 mg (see section 3.9).

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

This veterinary medicinal product may cause eye-irritation. Avoid hand-to-eye contact. If the veterinary medicinal product comes into contact with the eyes, rinse immediately and thoroughly with clean water.

This veterinary medicinal product may be harmful upon ingestion, and cause adverse effects such as nausea and vomiting. Avoid oral ingestion including hand-to-mouth contact. To avoid accidental ingestion, particularly by a child, unused tablet parts should be returned to the open blister space and inserted back into the carton. Store in a closed cabinet. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

Wash hands thoroughly, immediately after breaking or handling tablets.

To the physician:

An intravenous administration of isotonic sodium chloride (0.9%) will rapidly eliminate bromide ions in humans.

Special precautions for the protection of the environment:

Not applicable.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

3

Use during pregnancy, lactation or lay

The safety of the veterinary medicinal product has not been established during pregnancy and lactation.

Pregnancy and lactation:

Laboratory studies have not produced any evidence of adverse effects of potassium bromide on reproduction at non-maternotoxic doses. Use only according to the benefit-risk assessment by the responsible veterinarian.

Potassium bromide crosses the placental barrier. Since bromide may be excreted into milk, monitor suckling puppies for somnolence/sedative effects; if necessary, consider early weaning, or an artificial suckling method.

3

Interactions

Due to the competition between chloride ions and bromide ions for reabsorption by the kidneys, any major change in chloride intake can modify serum bromide concentrations which are directly correlated to treatment efficacy and the occurrence of adverse reactions. A reduction in chloride intake (low sodium diet) can cause a rise in serum bromide levels and increase the likelihood of bromide intoxication (see section 3.10). An increase in chloride intake (high salt diet) can cause a fall in serum bromide levels which could lead to seizures. Where possible, the diet of treated dogs should therefore not be altered. Seek veterinary advice before making any change to the dog's diet.

On biochemistry profiles serum chloride concentrations are often falsely elevated because the assays cannot distinguish between chloride and bromide ions.

Loop diuretics such as furosemide can increase bromide excretion and lower the efficacy of the treatment (risk of recurrence of seizures) if the dose is not adjusted.

Administration of fluids or drug formulations containing chloride can lower serum bromide concentrations.

Bromide is synergistic with other GABA-ergic drugs such as phenobarbital.

3

Overdose

Clinical signs of bromide toxicity (e.g. ataxia, somnolence) can occur in dogs with renal insufficiency or when a very high dose of bromide is administered. If overdose is suspected, the dosage should be reduced immediately, with close monitoring of serum bromide concentrations in order to establish an appropriate therapeutic concentration. Dose and serum bromide levels at which intolerance is observed vary between dogs. In cases of overdose requiring medical attention, administer 0.9% sodium chloride solution intravenously to reduce serum bromide concentrations.

3

Special warnings

The concentration of bromide in serum, the clinical response and the therapeutic effect of administration of the veterinary medicinal product may vary between individuals (see section 3.9). The presence of cluster seizures/status epilepticus, due to the severity of the seizure activity, is often associated with poor response to anti- epileptic treatment. In these cases, remission (seizure freedom) may be difficult to achieve.

For dogs with normal hepatic function, phenobarbital is generally considered the first- choice antiepileptic drug. However, potassium bromide can be recommended as alternative, especially in dogs with hepatic dysfunction or in dogs with concurrent disorders requiring life-long administration of potentially hepatotoxic medications, since potassium bromide is not metabolised in the liver (see section 4.3). A high chloride intake can increase the elimination of bromide (see section 3.8). An increase in the dog’s salt intake may require an adjustment in bromide dose. The salt content of a dog’s diet during the treatment period should be maintained at a stable level. It is advisable not to change the dog’s diet during therapy.

3

Withdrawal period

Not applicable.

3

Incompatibilities

Not applicable.

3

Immediate packaging

PVC/PVDC/Aluminium blisters

Cardboard box containing 60 or 120 tablets (4 or 8 blisters with 15 tablets each)

Not all pack sizes may be marketed.

3

Storage

Store below 30 °C.

After piercing a blister, replace unused tablet parts into the blister and place the blister back into the carton. Remaining tablet portions should be given at the next administration.

3

Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 4 years

3

Disposal of unused product

Medicines should not be disposed of via wastewater.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

3

Additional information

Vm 54982/4008

8 DATE OF FIRST AUTHORISATION

05 March 2021

9 DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

November 2025

10 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCT

Veterinary medicinal product subject to prescription.

Find more product information by searching for the ‘Product Information Database’ on www.gov.uk.

3

Registration holder

Domes Pharma

3