SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Epiphen Solution 4% w/v, Oral drops for dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substance: Phenobarbital 4.0% w/v

Qualitative composition of excipients and other constituents

Ethanol

Propylene glycol

Deionised water

A clear, colourless, slightly viscous liquid.

3. CLINICAL INFORMATION

3.1 Target species

Dogs

3.2 Indications for use for each target species

Phenobarbital is an antiepileptic agent for use in the control of epilepsy in the dog.

3.3 Contraindications

Not for use in pregnant animals or nursing bitches.

Do not use in animals with impaired hepatic function.

Do not use in cases of hypersensitivity to the active substance, to any other barbiturates or to any of the excipients.

Do not use in animals with serious renal and/or cardiovascular/respiratory disorders.

3.4 Special warnings

The decision to start antiepileptic drug therapy with phenobarbital should be evaluated for each individual case and depends on number, frequency, duration and severity of seizures in dogs.

To achieve successful therapy, administration of drops should occur at the same time(s) each day and should be co-ordinated with feeding times in a consistent manner.

Withdrawal or transition from other types of antiepileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures. Some dogs are free of epileptic seizures during the treatment, but some dogs show only a seizure reduction, and some dogs are considered to be non-responders.

3.5 Special precautions for use

Special precautions for safe use in the target species:

Caution is recommended in animals with:

• impaired hepatic and renal function

• hypovolemia, anaemia and

• cardiac or respiratory dysfunction

The chance of hepatotoxic side effects can be diminished or delayed using the minimum effective dose. Monitoring of hepatic parameters is recommended in case of a prolonged therapy.

It is recommended to assess the clinical pathology of the patient 2-3 weeks after start of treatment and afterwards every 4-6 months, e. g. measurement of hepatic enzymes and serum bile acids. It is important to know that the effects of hypoxia etc. do cause increased levels of hepatic enzymes after a seizure.

Phenobarbital may increase the activity of serum alkaline phosphatase and transaminases. These may demonstrate non-pathological changes but could also represent hepatotoxicity. Therefore, in the case of suspected hepatotoxicity, liver function tests are recommended.

Treating dogs with phenobarbital may lower TT4 or FT4 serum levels, however this may not be an indication of hypothyroidism. Treatment with thyroid hormone replacement should only be started if there are clinical signs of the disease.

In stabilised epileptic patients, it is not recommended to switch between phenobarbital formulations. However, if this cannot be avoided then additional caution should be taken. This includes more frequent plasma concentration sampling to ensure that therapeutic levels are maintained. Monitoring for increased side effects and for hepatic dysfunction should be conducted more regularly until stabilisation is confirmed.

A wide therapeutic range of phenobarbital concentration in the serum of 15 mg/l to 40 mg/l is often stated. Optimal seizure control is achieved in most dogs with a serum phenobarbital concentration of between 25−30 mg/l. High serum concentrations of more than 35 mg/l should be avoided due to increased risk of hepatotoxicity. Below these ranges, in dogs with good seizure control, no change of dose may be necessary, as the concentration may be sufficient for that individual. As a general guide, serum phenobarbital concentration should be the lowest to achieve a decrease in seizure frequency of greater than 50%, or absence of seizures where possible, without intolerable side effects.

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

Flammable, keep away from sources of ignition. Do not smoke.

People with known hypersensitivity to phenobarbital or other barbiturates should avoid contact with this veterinary medicinal product.

Personal protective equipment consisting of disposable gloves should be worn when handling the veterinary medicinal product.

Phenobarbital is a teratogen and developmental neurotoxicant and transfers to breast milk. The veterinary medicinal product should not be administered by pregnant women, women intending to become pregnant or whose pregnancy status is unknown, as well as lactating women.

Ingestion of phenobarbital can cause neurotoxicity which may prove fatal. Take utmost care that children do not come into any contact with the veterinary medicinal product. Children are particularly at risk of intoxication. To prevent accidental ingestion of phenobarbital, the vial should be closed immediately after withdrawing the required number of drops for one administration. The vial should be stored in a safe place out of the sight and reach of children.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. If possible, the physician should be informed about the time and amount of ingestion, as this information may help to ensure that appropriate treatment is given.

Wash hands after use.

Special precautions for the protection of the environment:

Not applicable.

3.6 Adverse events

Dogs:

Uncommon (1 to 10 animals / 1,000 animals treated):	Elevated serum alkaline phosphatase (ALP)6,8,, elevated alanine aminotransferase (ALT)6,8,, elevated aspartate aminotransferase (AST)6,8
Rare (1 to 10 animals / 10,000 animals treated):	Ataxia1,7,8, somnolence1,8, wobbliness1,8 Listless1,8, polydipsia3,8 Hyperexcitation2,8 Polyphagia3,8 Polyuria3,8 Hypoalbuminaemia6,8 Sedation7,8
Very rare (<1 animal / 10,000 animals treated, including isolated reports):	Hepatic disorder4,8 (hepatotoxicity4,8) Bone marrow disorder8 (decreased stem cells8) Neutropenia8, anaemia8, pancytopenia (immunotoxic)8 Dermatitis (necrolytic)5,8 Behavioural disorder, aggression8

¹At the start of treatment. In some cases, these effects may persist for the entire duration of treatment

²Paradoxical, particularly after first starting therapy. As this hyperexcitability is not linked to overdosage, no reduction of dosage is needed

³These effects are usually transitory and disappear with continued medication ⁴At doses over 20mg/kg/day or when serum phenobarbital levels are high (see special precautions for use)

⁵Superficial

⁶These may demonstrate non-pathological changes, but could also represent hepatotoxicity, so liver function tests are recommended (see section 3.5)

⁷May very rarely become significant concerns as serum levels reach the higher end of the therapeutic range.

⁸If adverse effects are severe, it is recommended to decrease the daily dose

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 the national competent authority via the national reporting system. See the package leaflet for respective contact details.

3.7 Use during pregnancy, lactation or lay

Pregnancy:

Use only according to the benefit-risk assessment by the responsible veterinarian.

Studies in laboratory animals have indicated that phenobarbital has an effect during prenatal growth, in particular causing permanent changes in neurological and sexual development. Neonatal bleeding tendencies have been associated with phenobarbital treatment during pregnancy. In case of pregnancy, the risk that the medication may cause an increase in the number of congenital defects must be weighed up against the risk of suspending treatment during pregnancy.

Discontinuation of treatment is not advised, but the dosage should be kept as low as possible.

Phenobarbital crosses the placenta and, at high doses (reversible), withdrawal symptoms cannot be ruled out in newborns.

The safety of the veterinary medicinal product has not been proven during pregnancy in dogs.

Lactation:

Use only according to the benefit-risk assessment by the responsible veterinarian.

Phenobarbital is excreted in small amounts in breast milk and during nursing pups should be monitored carefully for undesired sedative effects. Weaning early may be an option. If somnolence/sedative effects (that could interfere with suckling) appear in nursing newborns, an artificial suckling method should be chosen.

The safety of the veterinary medicinal product has not been proven during lactation in dogs.

3.8 Interaction with other medicinal products and other forms of interaction

Phenobarbital may reduce the activity of some drugs by increasing the rate of metabolism through induction of drug-metabolising enzymes in liver microsomes.

A therapeutic dose of phenobarbital for antiepileptic therapy can significantly induce plasma protein (such as α1acid glycoprotein, AGP), which bind drugs. Therefore, special attention must be paid to the pharmacokinetics and doses of drugs simultaneously administered.

The plasmatic concentration of cyclosporine, thyroid hormones and theophylline is decreased in the case of concurrent administration of phenobarbital. The effectiveness of these substances is diminished, too.

Concurrent use with potassium bromide increases the risk of pancreatitis.

Concurrent use with other drugs having a central depressive effect can result in an increase of the effect of central depressive drugs.

Phenobarbital may enhance the metabolism of, and therefore decrease the effect of, antiepileptics, chloramphenicol, corticosteroids, doxycycline, beta blockers and metronidazole.

The reliability of oral contraceptives is lower.

Phenobarbital may decrease the blood concentration of griseofulvin by reducing its absorption and/or inducing hepatic microsomal enzymes.

The following drugs can decrease the convulsive threshold: quinolones, high doses of β-lactam antibiotic, theophylline, aminophylline, cyclosporine and propofol for example). Medications which may alter the seizure threshold should only be used if really necessary and when no safer alternative exists.

Use of phenobarbital in conjunction with primidone is not recommended as primidone is predominantly metabolised to phenobarbital.

3.9 Administration routes and dosage

The required dosage will differ to some extent between individuals and with the nature and severity of the disorder.

Dogs should be dosed orally, starting with a dose of 2.5 - 5.0 mg/kg (0.06 - 0.125ml per kg) bodyweight per day. The dose should be divided and administered twice daily using the 2ml syringe provided. 1ml contains 40mg of phenobarbital.

DOSAGE GUIDE

Weight of dog	Volume of Epiphen Solution	Dosage range mg/kg
1 - 1.5 kg	0.1ml	2.7 – 4.0
2 – 3 kg	0.2ml	2.7 – 4.0
4 – 5 kg	0.4ml	3.2 – 4.0
6 - 9 kg	0. 7ml	3.1 – 4.7
10 – 15 kg	1.2ml	3.2 – 4.8
16 – 20 kg	1.6ml	3.2 – 4.0

Steady state serum concentrations are not reached until 1 - 2 weeks after treatment is initiated. The full effect of the medication does not appear for two weeks and doses should not be increased during this time.

If seizures are not being controlled, the dosage may be increased by 20% at a time, with associated monitoring of serum phenobarbital levels. The phenobarbital serum concentration may be checked after steady state has been achieved, and if it is less than 15 µg/ml the dose may be adjusted accordingly. If seizures recur the dose may be raised up to a maximum serum concentration of 40 µg/ml (see special precautions for use). High plasma concentrations may be associated with hepatotoxicity. Blood samples should be taken at the same time to allow plasma phenobarbital concentration to be determined preferably during trough levels, shortly before the next dose of phenobarbital is due.

3.10 Symptoms of Overdose (and where applicable, emergency procedures and antidotes)

Overdosage may result in coma, severe respiratory and cardiovascular depression, hypotension and shock leading to renal failure and death.

Following the recent ingestion of an overdose, the stomach may be emptied by lavage.

The prime objectives of management are then intensive symptomatic and supportive therapy with particular attention being paid to the maintenance of cardiovascular, respiratory and renal functions and to the maintenance of the electrolyte balance.

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.

3.12 Withdrawal periods

Not applicable.

4. PHARMACOLOGICAL INFORMATION

4.1 ATCvet code: QN03AA02

The antiepileptic effects of phenobarbital are probably the result of at least two mechanisms: - Decreased monosynaptic transmission, which presumably results in reduced neuronal excitability and an increase in the motor cortex's threshold for electrical stimulation.

After oral administration of phenobarbital to dogs, the drug is rapidly absorbed, and maximal plasma concentrations are reached within 4 - 8 hours. Bioavailability is between 86% - 96%. About 45% of the plasma concentration is protein bound. Metabolism is by aromatic hydroxylation of the phenyl group in the para position, and about one third of the drug is excreted unchanged in the urine. Elimination half-lives vary considerably between individuals and range from about 40 - 90 hours.

5. PHARMACEUTICAL PARTICULARS

5.1 Major incompatibilities

None known.

5.2 Shelf life

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

5.3 Special precautions for storage

Do not store above 25ºC Protect from light.

Keep the container tightly closed.

5.4 Nature and composition of immediate packaging

30 ml presentation in a carton

• amber glass vial of type II

• polyethylene syringe applicator

• medium density child proof polyethylene cap

• 2 ml polypropylene graduated syringe

A cardboard carton containing a 100 ml high density polyethylene bottle with an integral syringe adaptor insert closed with a child resistant cap. A 1.5ml polyethylene syringe barrel with graduated polystyrene plunger is also supplied.

A cardboard carton containing a 250 ml amber glass bottle closed with a child resistant cap.

Not all pack sizes may be marketed.

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

Medicines should not be disposed of via wastewater.

Any unused product must be destroyed in accordance with the Misuse of Drugs Regulations (2001).

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.

6. NAME OF THE MARKETING AUTHORISATION HOLDER

Vetoquinol UK Limited

7. MARKETING AUTHORISATION NUMBER

Vm 08007/5018

8. DATE OF FIRST AUTHORISATION

16 July 2001

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

August 2026

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.

Gavin Hall Approved: 09 September 2026