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PHENOBARBITONE 30 MG TABLETS

Active substance(s): PHENOBARBITONE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Phenobarbitone 30 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 30 mg of phenobarbitone (phenobarbital).
For excipients, see 6.1.

3

PHARMACEUTICAL FORM
Tablet.
White normal convex tablets engraved with the company logo on one side and
A061 on then other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Phenobarbitone tablets are recommended in the treatment of grand mal and
focal epilepsies.

4.2

Posology and method of administration
ADULTS.
Anticonvulsant: 60 to 200 mg per day (average 90 mg/day) in divided doses.
The dose should not exceed 600 mg in 24 hours.
CHILDREN AND ELDERLY:
Child: 5-8mg/kg daily
Elderly: Phenobarbital clearance diminishes in the elderly. Therefore the
dose of phenobarbital is usually lower in elderly patients.

Route of administration: Oral

4.3

Contraindications
Hypersensitivity to barbiturates or to any of the excipients
Acute intermittent porphyria
Patients with no previous barbiturates therapy
Insomnia caused by pain
Pregnancy and lactation
Children especially hyperkinetic
Severe hepatic and renal dysfunction
Elderly and debilitated patients
Patients with history of drug or alcohol abuse
Idiosyncrasy to barbiturates.
Severe respiratory depression

4.4

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.
Administration of Phenobarbitone to the elderly may result in paradoxical
excitement, restlessness and confusion.

Administration to children may result in irritability and hyperexcitability.
Chronic administration for prophylaxis against epilepsy may result in folate
deficiency. Caution should be exercised in patients with impaired hepatic,
renal and respiratory functions. (should be avoided if severe). Central nervous
system depressant effect of phenobarbitone may be additive with that of other
CNS depressants including alcohol dependence and tolerance. Prolonged use
may result in the dependence of the alcohol-barbiturate type and particular
care should be taken in treating patients with a history of drug abuse or
alcoholism.
Abrupt withdrawal may precipitate a serious withdrawal syndrome (rebound
insomnia, anxiety, tremor, dizziness, nausea, fits and delirium).
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.

4.5

Interaction with other medicinal products and other forms of interaction
Effects on Phenobarbital
Effects of phenobarbital on
other medicines
• Alcohol – concurrent administration Phenobarbital increases the rate of
reducing
serum
with alcohol may lead to an additive metabolism
CNS depressant effect. This is likely concentrations of the following drugs:
with concurrent administration with • Anti-arrhythmics – disopyramide and
other CNS depressants.
quinidine loss of arrhythmia control is
possible.
Plasma
levels
of
• Anaesthetics - when used concurrently
antiarrhymics should be monitored, if
with phenobarbitone may increase the
phenobarbital is added or withdrawn.
CNS depressant effects of either of
Changes in dosage may be necessary.
these medications or phenobarbitone
• Antidepressants – including MAOIs, • Antivirals – phenobarbital possibly
reduces plasma levels of abacavir,
SSRIs and tricyclics may antagonise
amprenavir, darunavir, lopinavir,
the
antiepileptic
activity
of
indinavir, nelfinavir, saquinavir.
phenobarbital by lowering the
convulsive threshold
• Anxiolytics
and
Hypnotics

clonazepam.
• Antiepileptics - Increased sedative
effects may occur with phenytoin, • Aprepitant – phenobarbital possibly
oxcarbazepine and sodium valproate
reduces plasma concentration of
aprepitant.
• Vigabatrin
possibly
decreases
phenobarbital plasma concentrations.
• Beta-blockers – metoprolol, timolol
and possibly propranolol.
• Antipsychotics – concurrent use of
chlorpromazine and thioridazine with • Cardiac Glycosides – blood levels of
phenobarbital can reduce the serum
digitoxin can be halved by concurrent
levels of either drug.
use.







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 possibly reduced.
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 John’s wort.








Cytotoxics – phenobarbital possibly
reduces the plasma levels of etoposide
or irinotecan.
Diuretics – concomitant use with
eplerenone should be avoided.
Enzyme induction - Phenobarbitone
may induce liver microsomal enzymes
and the rate of metabolism of certain
drugs can be increased and serum
concentrations of the following drugs
may be reduced: paracetamol;
coumarin
anticoagulants,
antiepileptics
(phenytoin,
carbamazepine,
lamotrigine,
phenylbutazone,
tiagabine,
zonisamide, primidone and possibly
ethosuxamide); systemic steroids
including oral contraceptives (which
may lead to contraceptive failure),
antifungals (griseofulvin,itraconazole,
posaconazole,
voriconazole,
aripiprazole) rifampicin, doxycycline,
folic acid, phenazone, phenothiazines,
tricyclic antidepressants, antibacterials
(chloramphenicol,
doxycycline,
metronidazole
and
rifampicin)
ciclosporin,
tacrolimus,
antidepressants (paroxetine, mianserin
and tricyclic antidepressants), calcium
channel
antagonists
(especially
felodipine,
isradipine,
diltiazem
verapamil, nimodipine and nifedipine
–may require an increase in dosage)
and theophylline. Avoid concomitant
use of telithromycin during and for 2
weeks after Phenobarbital.
Haloperidol- serum
levels are
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
been added.
Increases in the
methadone dosage may be necessary.
Montelukast.
Sodium oxybate – enhanced effects,






avoid concomitant use.
Theophylline – may require an
increase in theophylline dose.
Tibolone
Tropisetron
Vitamins – barbiturates possibly
increase requirements for vitamin D

Phenobarbital may interfere with some laboratory tests including metyrapone
test, phenlolamine tests and serum bilirubin estimation.

4.6

Fertility, Pregnancy and lactation
The use of phenobarbitone in pregnancy, especially the first and third
trimesters should be avoided unless it is considered to be essential.
Phenobarbitone should not be administered to expectant and nursing mothers
as it readily crosses the placental barrier and is distributed throughout foetal
tissue, highest concentrations are attained in the placenta, foetal liver and
brain. Neonatal bleeding may occur and prophylactic treatment with vitamin
k1 for mother before delivery (as well as for the neonate) is recommended.
Administration during pregnancy may result in congenital malformation.
Administration during third trimester results in neonatal bleeding, physical
dependence with withdrawal symptoms, neonates suffering from long-term
exposure in the uterus, the acute withdrawal syndrome of seizures and
hyperirritability has been reported to occur from birth to a delayed onset of up
to 14 days.
Patients taking phenobarbitone should be adequately supplemented with folic
acid before conception and during pregnancy.
Phenobarbitons is excreted in breast milk with resultant depression in the
infant. Breast feeding is therefore not advisable.

4.7

Effects on ability to drive and use machines
Administration of Phenobarbitone results in drowsiness, dizziness and ataxia
therefore patients taking this drug should not drive or operate machinery.

4.8

Undesirable effects
“For this product there is no modern clinical documentation which can be used
as support for determining the frequency of adverse reactions”.
Blood & lymphatic
system disorders

Frequency
Unknown

megaloblastic anaemia (due to folate
deficiency),
agranulocytosis,

system

Frequency
Unknown

Metabolism
&
Nutrition disorders
Psychiatric
disorders

Frequency
Unknown
Frequency
Unknown

Immune
disorders

Nervous
disorders

system Frequency
Unknown
Frequency
Unknown
Frequency
& Unknown

thrombocytopenia
Antiepileptic hypersensitivity syndrome
(drug rash with eosinophilia and
systemic symptoms - features include
fever,
rash,
lymphadenopathy,
lymphocytosis,
eosinophilia,
haematological abnormalities, hepatic
and other organ involvement including
renal and pulmonary systems which
may become life threatening)
osteomalacia, rickets
Paradoxical
reaction
(unusual
excitement),
hallucinations,
restlessness and confusion in the
elderly, abnormal behaviour, mental
depression, memory and cognitive
impairment,
drowsiness,
lethargy,
suidcidal ideation. Chronic use even in
therapeutic doses may result in
psychiatric or physical dependence.
Hyperactivity, ataxia, nystagmus

Vascular disorders

Hypotension

Respiratory,
thoracic
mediastinal
disorders
Frequency
Hepatobiliary
Unknown
disorders
Skin
and Frequency
Unknown
subcutaneous
tissue disorders
Rare

Respiratory depression

General
& Frequency
administration site Unknown
disorders

Hepatitis, cholestasis
Allergic skin reactions (maculopapular,
morbilliform or scarlatiniform rashes)
Serious skin reactions such as
exfoliative
dermatitis,
erythema
multiforme, toxic epidermal necrosis or
Stevens-Johnson syndrome
Abrupt withdrawal of the drug may
result in severe abstinence syndrome,
which includes grand mal seizures and
delirium. Withdrawal should therefore
be cautious and gradual.
Tolerance to the hypnotic effects of
phenobarbitone may also occur
following prolonged administration.

4.9

Overdose
Toxicity varies between patients; tolerance will develop with chronic use.
Features of poisoning are to be expected after ingestion of 1g in adults.
Features:
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.
Management:
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
hyperkalaemia.
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.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic
classification
ATC code

: Antiepileptics; Barbiturates and
Derivatives - phenobarbital
: N03A A02

Phenobarbitone is a barbiturate with hypnotic, sedative and anticonvulsant
properties. It is a non selective depressant of the CNS, capable of producing all
levels of CNS mood alteration from excitement to mild sedation, hypnosis and
deep coma.
In sufficiently high therapeutic doses, barbiturates induce anaesthesia. Studies
carried out indicate that sedative, hypnotic and anticonvulsant effects of
barbiturates may be related to their ability to enhance and/or mimic the
inhibitory synaptic action of gamma aminobutyric acid (GABA).
Sedative and hypnotic effect of phenobarbitone is achieved by depression of
the sensory cortex, decreasing motor activity and altering cerebral function
producing drowsiness, sedation and hypnosis. It appears to act at the level of
the thalamus where they inhibit ascending conduction in the reticular

formation; thus interfering with the transmission of impulses to the cortex.
Anticonvulsant property of phenobarbitone is achieved by depressing mono
synaptic and polysynaptic transmission in the CNS. Threshold for electrical
stimulation of the motor cortex is also increased. Phenobarbitone lowers serum
bilirubin concentrations probably by induction of glucuronyltransferase, the
enzyme which conjugates bilirubin.

5.2

Pharmacokinetic properties
Phenobarbitone is readily absorbed from the gastro-intestinal tract. The
absorption is increased if it is taken well diluted or on an empty stomach.
Phenobarbitone is relatively lipid insoluble when compared with other
barbiturates therefore it is distributed less rapidly than other barbiturates.
After ingestion it takes an hour or longer to act. Duration of action depends on
the rate of inactivation in the liver and rate of excretion unchanged in the
urine. Phenobarbitone is only about 40 per cent bound to plasma proteins and
is only partially metabolised in the liver. It has plasma half life of up to 75
hours in children and 100 hours in adults; this is increased in the elderly in
overdosage and in renal or hepatic disease.
About 25 per cent or more of a dose is excreted in the urine unchanged.
Excretion is increased in alkaline urine. Small amounts are excreted in the
bile.

5.3

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
Magnesium stearate
Maize starch
Pregelatinised maize starch

6.2

Incompatibilities
None stated.

6.3

Shelf life
60 months in polypropylene tubes, as packaged for sale.
60 months in amber glass bottles, as packaged for sale.
60 months in HDPP or HDPE containers, as packaged for sale.
24 months in A1/PVC blisters, as packaged for sale.

6.4

Special precautions for storage
Keep out of the reach of children.
Store in a cool, dry place.

6.5

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.
2.

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.

3.

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.

4.

Blister packs of aluminium/opaque PVC in pack sizes of 28, 30,42, 56, 60, 84, 90 or
112 tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal
None.

7

MARKETING AUTHORISATION HOLDER
Bristol Laboratories Limited
Unit 3, Canalside,
Northbridge road,
Berkhamsted HP4 1EG
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 17907/0512

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
08/02/2010

10

DATE OF REVISION OF THE TEXT
21/10/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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