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PHENOBARBITONE 60 MG TABLETS

Active substance(s): PHENOBARBITONE / PHENOBARBITONE / PHENOBARBITONE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Phenobarbitone 60 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 60 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
A063 on then other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
The treatment and control of all forms of epilepsy, except absence seizures.
Phenobarbital should only be used in the treatment of febrile convulsions in
exceptional circumstances.

4.2

Posology and method of administration
Posology

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
4.3

Contraindications
Phenobarbital should not be given to patient with:





4.4

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:

4.5



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



Renal impairment



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
the
antiepileptic
activity
of
phenobarbital by lowering the
convulsive threshold
Antiepileptics – Phenobarbital plasma
concentrations increased by phenytoin,
oxcarbazepine
and
sodium
valproate.Vigabatrin
possibly
decreases
phenobarbital
plasma
concentrations.
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
other medicines
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,
doxycycline,
metronidazole
and
rifampicin. Avoid concomitant use of
telithromycin during and for 2 weeks
after Phenobarbital.
• Anticoagulants.
• Antidepressants

paroxetine,
mianserin
and
tricyclic
antidepressants.
• Antiepileptics

carbamazepine,
lamotrigine, tiagabine, zonisamide,
primidone and possibly ethosuxamide.





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.




















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 voriconazole.
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 propranolol.
Calcium
channel
blockers

phenobarbital causes reduced levels of
felodipine,
isradipine,
diltiazem
verapamil, nimodipine and nifedipine
and and increase in dosage may be
required.
Cardiac Glycosides – blood levels of
digitoxin can be halved by concurrent
use.
Ciclosporin or tacrolimus
Corticosteroids
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 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.
Oestrogens – reduced contraceptive
effect
Progestogens – reduced contraceptive
effect
Sodium oxybate – enhanced effects,
avoid concomitant use.
Theophylline – may require an
increase in theophylline dose.
Thyroid hormones – may increase
requirements for thyroid hormones in
hypothyroidism.
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
Pregnancy
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.
Breast-feeding

Phenobarbitone is excreted in breast milk and there is a small risk of neonatal
sedation. Breast feeding is therefore not advisable.
4.7

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.

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

Metabolism
&
Nutrition disorders

Frequency
Unknown

Frequency
Unknown

Psychiatric
disorders

Nervous
disorders

system Frequency
Unknown
Frequency
Unknown
Frequency
& Unknown

megaloblastic anaemia (due to folate
deficiency),
agranulocytosis,
thrombocytopenia
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.
Paradoxical
reaction
(unusual
excitement),
hallucinations,
restlessness and confusion in the
elderly, mental depression, memory
and cognitive impairment, drowsiness,
lethargy,
Hyperactivity,
ataxia,
nystagmus,
behavioural disturbances in children

Cardiac disorders

Hypotension

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

Respiratory depression

Very Rare

Hepatitis, cholestasis
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

General
& Frequency
administration site Unknown
disorders

(TEN) or Stevens-Johnson syndrome
(SJS) have been reported (see section
4.4)
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:
www.mhra.gov.uk/yellowcard
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

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.
5.2

Pharmacokinetic properties
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.

5.3

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.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
Magnesium stearate
Maize starch

6.2

Incompatibilities
None stated.

6.3

Shelf life
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.

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 17907/0513

9

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

10

DATE OF REVISION OF THE TEXT
31/10/2016

Expand Transcript

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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