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PHENOBARBITONE 60 MG TABLETS
Active substance(s): PHENOBARBITONE / PHENOBARBITONE / PHENOBARBITONE
NAME OF THE MEDICINAL PRODUCT
Phenobarbitone 60 mg Tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 60 mg of phenobarbitone (phenobarbital).
For excipients, see 6.1.
White normal convex tablets engraved with the company logo on one side and
A063 on then other side.
The treatment and control of all forms of epilepsy, except absence seizures.
Phenobarbital should only be used in the treatment of febrile convulsions in
Posology and method of administration
Adults: 60-180mg at night
Child: 5-8mg/kg daily
Elderly: Phenobarbital clearance diminishes in the elderly. Therefore the dose
of phenobarbital is usually lower in elderly patients.
The dose of phenobarbital should be adjusted to meet the needs of individual
patients. This usually requires plasma concentration of 15 to 40
micrograms/ml (65 to 170 micromoles/litre).
Method of administration:
For oral administration
Phenobarbital should not be given to patient with:
Hypersensitivity to phenobarbital, other barbiturates or to any of the
excipients listed in section 6.1.
Acute intermittent porphyria
Severe hepatic and renal impairment
Severe respiratory depression
Special warnings and precautions for use
Suicidal ideation and behaviour have been reported in patients treated with
anti-epileptic agents in several indications. A meta-analysis of randomised
placebo controlled trials of anti-epileptic drugs has also shown a small
increased risk of suicidal ideation and behaviour. The mechanism of this risk
is not known and the available data do not exclude the possibility of an
increased risk for Phenobarbitone.
Therefore patients should be monitored for signs of suicidal ideation and
behaviours and appropriate treatment should be considered. Patients (and
caregivers of patients) should be advised to seek medical advice should signs
of suicidal ideation or behaviour emerge.
Steven-Johnson syndrome and toxic epidermal necrolysis
Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and
toxic epidermal necrolysis (TEN) have been reported with the use of
phenobarbital. Patients should be advised of the signs and symptoms and
monitored closely for skin reactions. The highest risk for occurrence of SJS or
TEN is within the first weeks of treatment.
If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with
blisters or mucosal lesions) are present, Phenobarbital treatment should be
discontinued. The best results in managing SJS and TEN come from early
diagnosis and immediate discontinuation of any suspect drug. Early
withdrawal is associated with a better prognosis.
If the patient has developed SJS or TEN with the use of phenobarbital,
phenobarbital must not be re-started in this patient at any time.
Care should be used in the following situations:
Prolonged use may result in dependence of the alcohol-barbiturate type
and particular care should be taken in treating patients with a history of
drug abuse or alcoholism.
Sudden withdrawal should be avoided as severe withdrawal syndrome
(rebound insomnia, anxiety, tremor, dizziness, nausea, fits and
delirium) may be precipitated.
Patients with the rare hereditary problems of galactose intolerance, the
lapp lactase deficiency or glucose – galactose malabsorption should not
take this medicine
Respiratory depression (avoid if severe)
Acute chronic pain – paradoxical excitement may be induced or
important symptoms masked.
Young, debilitated or senile patients
Existing liver disease
Interaction with other medicinal products and other forms of interaction
Effects on Phenobarbital
Alcohol – concurrent administration
with alcohol may lead to an additive
CNS depressant effect. This is likely
with concurrent administration with
other CNS depressants.
Antidepressants – including MAOIs,
SSRIs and tricyclics may antagonise
phenobarbital by lowering the
Antiepileptics – Phenobarbital plasma
concentrations increased by phenytoin,
Antipsychotics – concurrent use of
chlorpromazine and thioridazine with
phenobarbital can reduce the serum
levels of either drug.
Folic acid – if folic acid supplements
Effects of phenobarbital on
Phenobarbital increases the rate of
metabolism reducing serum
concentrations of the following drugs:
• Anti-arrhythmics – disopyramide and
quinidine loss of arrhythmia control is
possible. Plasma levels of antiarrhymics should be monitored, if
phenobarbital is added or withdrawn.
Changes in dosage may be necessary.
• Antibacterials – chloramphenicol,
rifampicin. Avoid concomitant use of
telithromycin during and for 2 weeks
lamotrigine, tiagabine, zonisamide,
primidone and possibly ethosuxamide.
are given to treat folate deficiency,
which can be caused by the use of
phenobarbital levels may fall, leading
to decreased seizure control in some
patients (see section 4.6).
Phenobarbital is possibly reduced.
concentration of Phenobarbital is
perforatum) – the
phenobarbital can be reduced by
concomitant use of the herbal remedy
St John’s wort.
Antifungals – the antifungal effects of
griseofulvin can be reduced or even
Phenobarbital possibly reduces plasma
concentrations of itraconazole or
posaconazole. Avoid concomitant use
possibly reduces concentration of
Antivirals – phenobarbital possibly
reduces plasma levels of abacavir,
amprenavir, darunavir, lopinavir,
indinavir, nelfinavir, saquinavir.
Aprepitant – phenobarbital possibly
reduces plasma concentration of
Beta-blockers – metoprolol, timolol
and possibly propranolol.
phenobarbital causes reduced levels of
verapamil, nimodipine and nifedipine
and and increase in dosage may be
Cardiac Glycosides – blood levels of
digitoxin can be halved by concurrent
Ciclosporin or tacrolimus
Cytotoxics – phenobarbital possibly
reduces the plasma levels of etoposide
Diuretics – concomitant use with
eplerenone should be avoided.
approximately halved by concurrent
used with phenobarbital.
Hormone Antagonists – gestrinone
and possibly toremifene.
Methadone – levels can be reduced by
concurrent use of phenobarbital and
withdrawal symptoms have been
reported in patients maintained on
methadone when phenobarbital has
Increases in the
methadone dosage may be necessary.
Oestrogens – reduced contraceptive
Progestogens – reduced contraceptive
Sodium oxybate – enhanced effects,
avoid concomitant use.
Theophylline – may require an
increase in theophylline dose.
Thyroid hormones – may increase
requirements for thyroid hormones in
Vitamins – barbiturates possibly
increase requirements for vitamin D
Phenobarbital may interfere with some laboratory tests including metyrapone
test, phenlolamine tests and serum bilirubin estimation.
Fertility, pregnancy and lactation
Phenobarbital therapy in epileptic pregnant women presents a risk to the fetus
in terms of major and minor congenital defects such as congenital craniofacial,
digital abnormalities and, less commonly, cleft lip and palate. The risk of
teratogenic effects developing appears to be greater if more than one
antiepileptic drug is administered. The risk to the mother, however is greater if
phenobarbital is withheld and seizure control is lost. The risk: benefit balance,
in this case, favours continued use of the drug during pregnancy at the lowest
possible level to control seizures.
Patients taking Phenobarbital should be adequately supplemented with folic
acid before conception and during pregnancy (see section 4.5). Folic acid
supplementation during pregnancy can help to reduce the risk of neural defects
to the infant.
Phenobarbital readily crosses the placenta following oral administration and is
distributed throughout fetal tissue, the highest concentrations being found in
the placenta, fetal liver and brain. Adverse effects on neurobehavioral
development have also been reported.
Haemorrhage at birth and addiction are also a risk. Prophylactic treatment with
vitamin K1 for the mother before delivery (as well as the neonate) is
recommended, the neonate should be monitored for signs of bleeding.
Phenobarbitone is excreted in breast milk and there is a small risk of neonatal
sedation. Breast feeding is therefore not advisable.
Effects on ability to drive and use machines
Phenobarbital may impair the mental and/or physical abilities required for the
performance of potentially hazardous tasks such as driving a car or operating
machinery. Patients should be advised to make sure they are not affected
before undertaking any potentially hazardous tasks.
“For this product there is no modern clinical documentation which can be used
as support for determining the frequency of adverse reactions”.
Blood & lymphatic
megaloblastic anaemia (due to folate
There have been reports of decreased
bone mineral density, osteopenia,
osteoporosis and fractures in patients on
long-term therapy with phenobarbital.
The mechanism by which phenobarbital
affects bone metabolism has not been
restlessness and confusion in the
elderly, mental depression, memory
and cognitive impairment, drowsiness,
behavioural disturbances in children
Allergic skin reactions (maculopapular,
morbilliform or scarlatiniform rashes),
other skin reactions such as exfoliative
dermatitis, erythema multiforme
Serious cutaneous adverse reaction
(SCARs): Toxic epidermal necrosis
administration site Unknown
(TEN) or Stevens-Johnson syndrome
(SJS) have been reported (see section
Antiepileptic hypersensitivity syndrome
(features include fever, rash,
abnormalities, hepatic and other organ
involvement including renal and
pulmonary systems which may become
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme; website:
Toxicity varies between patients; tolerance will develop with chronic use.
Features of poisoning are to be expected after ingestion of 1g in adults.
Drowsiness, dysarthria, ataxia, nystagmus and disinhibition. There may also
be coma, cardiovascular collapse, cardiac arrest, hypotension, hypotonia,
hyproreflexia, hypothermia, hypotension and respiratory depression.
Barbiturates decrease gut motility, which may lead to slow onset and
worsening of symptoms or cyclical improvement and worsening of symptoms.
Consider activated charcoal (50g for an adult, 10-15g for a child under 5
years) if more than 10mg/kg body weight of phenobarbital has been ingested
within 1 hour, provided the airway can be protected. Repeat dose activated
charcoal is the best method of enhancing elimination of phenobarbital in
symptomatic patients. In severe hypotension dopamine or dobutamine can be
used. Treat rhabdomyolysis with urinary alkalinistion. Haemodialysis or
haemofiltration may be required for cases of acute renal or severe
Charcoal haemoperfusion is the treatment of choice for the majority of patients
with severe barbiturate poisoning who fail to improve, or who deteriorate
despite good supportive care.
: Antiepileptics; Barbiturates and
Derivatives - phenobarbital
: N03A A02
Phenobarbital is a long-acting barbiturate, which because of its depressant
effect on the motor cortex, is used in the treatment of epilepsy.
Phenobarbital has a widespread depressant action on cerebral function. It has
sedative effects and has some protective action against all varieties of human
partial and generalised epilepsy, with the exception of absence seizures.
Phenobarbital is also effective in preventing seizures in the corresponding
experimental animal models of epilepsy. In different studies phenobarbital
appears to have had inconsistent effects in suppressing experimental epileptic
foci, and epileptic after-discharges, but it inhibits synaptic transmission, at
least in the spinal cord. The drug's probable biochemical mechanism of action
is through prolonging the opening time of Cl- ion channels in postsynaptic
neuronal membranes. This effect causes membrane hyperpolarisation and thus
impairs nerve impulse propagation.
Phenobarbital also decreases intraneuronal Na+ concentrations, and inhibits
Ca2+ influx into depolarised synaptosomes. It raises brain serotonin levels,
and inhibits noradrenaline (norepinephrine) reuptake into synaptosomes.
These additional biochemical actions may contribute towards the
anticonvulsant effects of the drug.
Absorption - Phenobarbital is readily absorbed from the gastro-intestinal tract,
although it is relatively lipid – insoluble; peak concentrations are reached in
about 2 hours after oral administration.
Distribution – Phenobarbital is about 45 to 60% bound to plasma proteins.
Phenobarbital crosses the placental barrier and is distributed into breast milk.
Metabolism – The plasma half life is about 75 to 120 hours in adults but is
greatly prolonged in neonates, and shorter (about 21 to 75 hours) in children.
There is considerable interindividual variation in phenobarbital kinetics.
Phenobarbital is only partly metabolised in the liver.
Elimination - About 25% of a dose is excreted in the urine unchanged at
normal urinary pH.
Preclinical safety data
There are no pre-clinical safety data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.
List of excipients
36 months in polypropylene tubes, as packaged for sale.
36 months in amber glass bottles, as packaged for sale.
36 months in HDPP or HDPE containers, as packaged for sale.
24 months in A1/PVC blisters, as packaged for sale.
Special precautions for storage
Keep out of the reach of children.
Store in a cool, dry place.
Nature and contents of container
1. Opaque plastic containers composed of polypropylene tubes and polyethylene made
tamper-evident closures in pack sizes of 28, 30, 42, 50, 56, 60, 84, 90, 100, 112, 250,
500 or 1000 tablets.
Amber glass bottles with screw caps in pack sizes of 28, 30, 42, 50, 56, 60, 84, 90,
100, 112, 250, 500 or 1000 tablets.
Opaque plastic containers composed of either high density polypropylene or high
density polyethylene with a tamper-evident or child-resistant tamper-evident closure
composed of high density polyethylene with a packing inclusion of standard polyether
foam or polyethylene or polypropylene made filler in pack sizes of 28, 30, 42, 50, 56,
60, 84, 90, 100, 112, 250, 500 or 1000 tablets.
Blister packs of aluminium/opaque PVC in pack sizes of 28, 30,42, 56, 60, 84, 90 or
Not all pack sizes may be marketed.
Special precautions for disposal
MARKETING AUTHORISATION HOLDER
Bristol Laboratories Limited
Unit 3, Canalside,
Berkhamsted HP4 1EG
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
DATE OF REVISION OF THE TEXT
Source: Medicines and Healthcare Products Regulatory Agency
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