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PHENOBARBITAL ACTAVIS 60MG TABLETS
NAME OF THE MEDICINAL PRODUCT
Phenobarbital Actavis 60mg Tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Tablets for oral administration.
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 patients with:
• Known hypersensitivity to phenobarbital, other barbiturates or other
ingredients in the tablet
• Acute intermittent porphyia
• Severe respiratory depression
• Severe renal or hepatic impairment.
Special warnings and precautions for use
Suicidal ideation and behavior have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomized placebo
controlled trials of anti-epileptic drugs has also shown a small increased risk
of suicidal ideation and behavior. The mechanism of this risk is not known and
the available data do not exclude the possibility of an increased risk for
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 behavior 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:
• Patients with the rare hereditary problems of galactose intolerance, the
lapp lactase deficiency or glucose – galactose malabsorption should not take
• Respiratory depression (avoid if severe)
• Young, debilitated or senile patients
• Renal impairment
• Existing liver disease
• Sudden withdrawal should be avoided as severe withdrawal syndrome
(rebound insomnia, anxiety, tremor, dizziness, nausea, fits and delirium) may
• Acute chronic pain – paradoxical excitement may be induced or important
• Prolonged use may result in dependence of the alcohol-barbiturate type.
Care should be taken in treating patients with a history of drug abuse or
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
• Antidepressants – including MAOIs, SSRIs
and tricyclics may antagonise the antiepileptic
activity of phenobarbital by lowering the
• Antiepileptics - phenobarbital plasma
concentrations increased by oxcarbazepine,
phenytoin and sodium valproate. Vigabatrin
possibly decreases phenobarbital plasma
• Antipsychotics – concurrent use of
chlorpromazine and thioridazine with
phenobarbital can reduce the serum levels of
• Folic acid – if folic acid supplements are
given to treat folate deficiency, which can be
caused by the use of phenobarbital, the serum
phenobarbital levels may fall, leading to
decreased seizure control in some patients.
(see section 4.6).
• Memantine – the effect of Phenobarbital is
• Methylphenidate – plasma concentration of
Phenobarbital is possibly increased.
• St John’s wort (Hypericum perforatum) – the
effect of phenobarbital can be reduced by
concomitant use of the herbal remedy St
Effects of phenobarbital on other medicines
Phenobarbital increases the rate of metabolism
reducing serum concentrations of the following
• 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, doxycycline,
metronidazole and rifampicin. Avoid concomitant
use of telithromycin during and for 2 weeks after
• Antidepressants – paroxetine, mianserin and
• Antiepileptics – carbamazepine, lamotrigine,
tiagabine, zonisamide, primidone and possibly
• Antifungals – the antifungal effects of
griseofulvin can be reduced or even abolished by
concurrent use. Phenobarbital possibly reduces
plasma concentrations of itraconazole or
posaconazole. Avoid concomitant use of
• Antipsychotics – phenobarbital possibly reduces
concentration of aripiprazole.
• Antivirals – phenobarbital possibly reduces
plasma levels of abacavir, amprenavir, darunavir,
lopinavir, indinavir, nelfinavir, saquinavir.
• Anxiolytics and Hypnotics – clonazepam.
• Aprepitant – phenobarbital possibly reduces
plasma concentration of aprepitant.
• Beta-blockers – metoprolol, timolol and possibly
• Calcium channel blockers – phenobarbital causes
reduced levels of felodipine, isradipine, diltiazem,
verapamil, nimodipine and nifedipine and an
increase in dosage may be required.
Cardiac Glycosides – blood levels of digitoxin
can be halved by concurrent use.
Ciclosporin or tacrolimus.
Cytotoxics – phenobarbital possibly reduces the
plasma levels of etoposide or irinotecan.
Diuretics – concomitant use with eplerenone
should be avoided.
Haloperidol- serum levels are approximately
halved by concurrent used with phenobarbital.
Hormone Antagonists – gestrinone and possibly
Methadone – levels can be reduced by concurrent
use of phenobarbital and withdrawal symptoms
have been reported in patients maintained on
methadone when phenobarbital has been added.
Increases in the methadone dosage may be
Oestrogens – reduced contraceptive effect.
Progestogens – reduced contraceptive effect.
Sodium oxybate – enhanced effects, avoid
Theophylline – may require an increase in
Thyroid hormones-may increase requirements for
thyroid hormones in hypothyroidism.
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.
Phenobarbital is excreted into 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.
Blood and the lymphatic system disorders: megaloblastic anaemia (due to
folate deficiency), agranulocytosis, thrombocytopenia.
Metabolism and nutritional disorders: osteomalacia, rickets.
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 identified.
Psychiatric disorders: paradoxical reaction (unusual excitement),
hallucinations, restlessness and confusion in the elderly, mental
depression, memory and cognitive impairment, drowsiness, lethargy.
Nervous system disorders: hyperactivity, behavioural disturbances in
children, ataxia, nystagmus.
Cardiac disorders: hypotension.
Respiratory disorders: respiratory depression.
Hepato-bilary: hepatitis, cholestasis.
Skin and subcutaneous tissue disorders: allergic skin reactions
(maculopapular morbilliform or scarlatiniform rashes), other skin
reactions such as exfoliative dermatitis, erythema multiforme.
Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome
(SJS) and toxic epidermal necrolysis (TEN) have been reported (see
Frequency: very rare
General disorders and administration site conditions: antiepileptic
hypersensitivity syndrome (features include fever, rash, lymphadenopathy,
lymphocytosis, eosinophilia, haematological abnormalities, hepatic and
other organ involvement including renal and pulmonary systems which
may become life threatening).
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,
hyporeflexia, 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.
ATC CODE: 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 gastrointestinal 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 in 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 is no preclinical data of relevance to a prescriber which is additional to that
already included in other sections of the S.P.C.
List of excipients
Lactose BP, Starch BP, Talc BP, Stearic Acid BP.
Special precautions for storage
Store in a dry place below 20°C.
Nature and contents of container
The product is packed in Securitainers (High density polyethylene tub with low
density polypropylene lids), in quantities of 1000 tablets per pack.
Special precautions for disposal
No specific instructions. All medicines should be stored out of the reach of
MARKETING AUTHORISATION HOLDER
Actavis Group PTC ehf.
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
21st Sept 2005
DATE OF REVISION OF THE TEXT
Source: Medicines and Healthcare Products Regulatory Agency
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