Contra-indications
Do not use in animals with serious impaired hepatic function.
Do not use in animals with serious renal or cardiovascular disorders.
Do not use in dogs weighing less than 6 kg body weight.
Do not use in case of hypersensitivity to the active substance or to any other barbiturates or to any of the excipients.
Special warnings for each target species
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.
Some of the dogs are free of epileptic seizures during the treatment, but some of the dogs show only a seizure reduction, and some of the dogs are considered to be non-responders.
Special precautions for use in animals
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 an effective dose that is as low as possible. 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, liver function tests are recommended. Increased liver enzyme values do not require a dose reduction of phenobarbital if the serum bile acids are in the normal range.
In stabilised epileptic patients, it is not recommended to switch from other phenobarbital formulators to Epityl 60 mg tablets. 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. Withdrawal or transition from other types of anti-epileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures.
The tablets are flavoured. In order to avoid any accidental ingestion, store tablets out of reach of the animals
Special precautions to be taken by the person administering the veterinary medicinal product to animals
- Barbiturates can cause hypersensitivity. People with known hypersensitivity to barbiturates should avoid contact with the product.
- Accidental ingestion may cause intoxication and could be fatal, particularly for children. Take utmost care that children do not come in contact with the product.
- Phenobarbital is teratogenic and may be toxic to unborn and breastfeeding children; it may affect the developing brain and lead to cognitive disorders. Phenobarbital is excreted in breast milk. Pregnant women, women of childbearing age and women who are breastfeeding should avoid accidental ingestion and prolonged skin contact with the product.
- Keep this product in its original packaging to avoid accidental ingestion.
- It is advisable to wear disposable gloves during administration of the product to reduce skin contact.
- In case of accidental ingestion, seek medical attention immediately, advising medical services of barbiturate poisoning; 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.
- Each time an unused part-tablet is stored until next use, it should be returned to the open blister space and inserted back into the cardboard box.
- Wash hands thoroughly after use.
Adverse reactions
Dogs:
Very rare (<1 animal / 10,000 animals treated, including isolated reports): | Ataxia (incoordination) and sedation1 Paradoxical hyperexcitability (unusually excitable)2 Polyuria (increased urination), polydipsia (increased thirst) and polyphagia (increased appetite)3 Hepatotoxicity4 Pancytopenia and/or neutropenia5 Low free thyroxine (FT4) or low thyroxine (T4)6 |
1: During start of therapy these effects can occur but are usually transitory and disappear in most, but not all, patients with continued medication. Sedation and ataxia often become significant concerns as serum levels reach the higher ends of the therapeutic range.
2: Some animals can demonstrate a paradoxical hyperexcitability, particularly after first starting therapy. As this hyperexcitability is not linked to overdosage, no reduction of dosage is needed.
3: These effects can occur at average or higher therapeutic active serum concentrations; these effects can be diminished by limiting intake of food.
4: High plasma concentrations may be associated with hepatotoxicity.
5: Phenobarbital can have deleterious effects on stem cells from bone marrow. Consequences are immunotoxic pancytopenia and/or neutropenia. These reactions disappear after the treatment’s withdrawal.
6: Treating dogs with phenobarbital may lower their 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.
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 also the package leaflet for respective contact details.
Interaction with other medicinal products and other forms of interaction
A therapeutic dose of phenobarbital for antiepileptic therapy can significantly induce plasma proteins, (such as α1acid glycoprotein, AGP), which bind drugs. Phenobarbital may reduce the activity of some drugs by increasing the rate of metabolism through induction of drug‑metabolising enzymes in liver microsomes. Therefore special attention must be paid to the pharmacokinetics and doses of drugs simultaneously administered. The plasmatic concentration of a range of drugs (for example cyclosporine, thyroid hormones and theophylline) is decreased in the case of concurrent administration of phenobarbital. Concurrent use with other drugs having a central depressive action (like narcotic analgesics, morphinic derivatives, phenothiazines, antihistamines, clomipramine and chloramphenicol) can increase the effect of phenobarbital.
Cimetidine and ketoconazole are inhibitors of hepatic enzymes: concurrent use with phenobarbital can induce an increase of serum concentration of phenobarbital. Phenobarbital may decrease the absorption of griseofulvin.
Concurrent use with potassium bromide increases the risk of pancreatitis.
Use of phenobarbital tablets in conjunction with primidone is not recommended as primidone is predominantly metabolized to phenobarbital.
The following drugs can decrease the convulsive threshold: quinolones, high doses of β-lactam antibiotic, theophyllin, aminophyllin, cyclosporine and propofol for example). Medications which may alter the seizure threshold should only be used if really necessary and when no safer alternative exist.
Use during pregnancy, lactation or lay
Phenobarbital crosses the placental barrier and at higher doses (reversible) withdrawal symptoms in newborns cannot be excluded. Studies in laboratory animals have shown evidence of action of phenobarbital on prenatal growth, especially concerning sexual development. Neonatal bleeding tendencies have been associated with phenobarbital treatment during pregnancy. Administration of Vitamin K to the dam for 10 days before parturition may help to minimize these effects on the fetus.
The safety of the product has not been established during pregnancy of dogs. The benefits of treatment may be greater than the potential risks associated with epileptic seizures on the fetus (hypoxia and acidosis). Therefore, in case of pregnancy, termination of antiepileptic treatment is not recommended; however, the dose should be as low as possible.
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.
Use during pregnancy and lactation only according to the benefit/risk assessment by the responsible veterinarian.
Overdose (symptoms, emergency procedures, antidotes)
Symptoms of overdose are:
- depression of the central nervous system demonstrated by signs ranging from sleep to coma,
- respiratory problems,
- cardiovascular problems, hypotension and shock leading to renal failure and death.
In case of overdose remove ingested product from the stomach and give respiratory and cardiovascular support as necessary.
There is no specific antidote, but CNS stimulants, (like Doxapram) may stimulate the respiratory centre.