31/01/2012

Phenobarbital Elixir BP - electronic Medicines Compendium (eMC) - print fri

Tho n on & Ro

L d

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Phenobarbital Eli ir BP

1. NAME OF THE MEDICINAL PRODUCT

Phenoba bi al Eli i BP

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Phenoba bi al BP 0.3% /

3. PHARMACEUTICAL FORM
Eli i

4. CLINICAL PARTICULARS
4.1 Therapeutic indications A an an icon 4.2 Posolog O al REC OMMENDED DOSE AND DOSAGE SC HEDULE U al ad l dail do e: ae : 60-200mg phenoba bi al aken in 2 o 3 di ided po ion . ini iall 3-6mg pe kg bod fo e a di ec ed b eigh pe da aken in 2 o 3 di ided po ion . he p ac i ione l an in he ea men of all fo m of epilep e cep ab ence ei e .

and method of administration

C hild en: Label

4.3 Contraindications C on a-indica ed in pa ien i h kno n h pe en i i i o ba bi a e o an o he ing edien , i h e e e e pi a o dep e ion, i h e e el impai ed hepa ic o enal f nc ion, and in ca e of ac e in e mi en po ph ia. Al o in h pe kine ic child en. 4.4 Special arnings and precautions for use

S icidal idea ion and beha io ha e been epo ed in pa ien ea ed i h an i-epilep ic agen in e e al indica ion . A me a-anal i of andomi ed placebo con olled ial of an i-epilep ic d g ha ho n a mall inc ea ed i k of icidal idea ion and beha io . The mechani m of hi i k i no kno n and he a ailable da a do no e cl de he po ibili of an inc ea ed i k fo Phenoba bi al Eli i BP. The efo e pa ien ho ld be moni o ed fo ign of icidal idea ion and beha io and app op ia e ea men ho ld be con ide ed. Pa ien (and ca egi e of pa ien ) ho ld be ad i ed o eek medical ad ice ho ld ign of icidal idea ion o beha io eme ge.
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Phenobarbital Elixir BP - electronic Medicines Compendium (eMC) - print fri

Barbiturates are frequently used in suicidal attempts. In the presence of severe pain, barbiturates may fail to exert their hypnotic action and may cause wakefulness, excitement and delirium unless accompanied by an analgesic. Phenobarbital should be used with caution in the young, debilitated or senile patients and those with renal impairment, existing liver disease or respiratory depression (should be avoided if severe). 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. Avoid sudden withdrawal to prevent rebound seizures. 4.5 Interaction with other medicinal products and other forms of interaction The effects of phenobarbital are enhanced by concurrent administration of other sedatives, monoamine oxidase inhibitors and some tranquillizers and may be enhanced by anticholinesterases, sodium valproate, sulphonylurea, antidiabetics and tricyclic antidepressants. Increased sedative effects may occur with phenytoin and sodium valproate. The concommitant administration of barbiturates and alcohol may lead to an additive C NS depressant effect, may produce very serious respiratory depression and a lowering of the lethal dose of phenobarbital. The effects of other depressants of the central nervous system such as anaesthetics, antihistamines and narcotic analgesics may also be enhanced. The effects of phenobarbital may be diminished by rendering the urine alkaline and possibly by antidepressants, antipsycotics, reserpine and folic acid. Phenobarbital may enhance the activity of methotrexate, cyclophosphamide and sulphonylureas. Phenobarbital increases the rate of metabolism of many drugs by induction of drug-metabolising enzymes in liver microsomes. This may result in a reduction in activity. Drugs affected include carbamazepine, coumarin anticoagulants, doxycyline, folic acid, phenylbutazone, phenazone, phenytoin, corticosteroids and other systemic steroids including oral contraceptives (which may lead to oral contraceptive failure), lamotrigine, rifampicin, phenothiazines, tricyclic antidepressants, calcium channel antagonists (especially felodipine, verapamil, nimodipine and nifedipine may require an increase in dosage) and theophylline. The activity of griseofulvin may be reduced if it is given by mouth with phenobarbital. Plasma concentrations are reduced when used with alprenolol, amfebutamone, chloramphenicol, clonazepam, ciclosporin, dicoumarol, digitoxin, disopyramide, doxorubicin, ethosuximide, etopside, fenoprofen, folate, gestrinone, haloperidol, indinavir, itraconazole, lidocaine, methadone, metoprolol, metronidazole, mianserin, montelukast, nelfinavir, paroxetine, phenothiazines (eg. chlorpromazine, mesoridazine, thiodorazine), phenylbutazone, pyridoxine, propafenone, propranolol, quinidine, saquinavir, sodium valproate, tibolone, tiagabine, topisetron, timolol, toremifene and tricyclic antidepressants (eg. imipramine, amitriptyline). Increased phenobarbital levels may occur when used concomitantly with chloramphenicol, dextropropoxyphene, furosemide, quinine and the influenza vaccine. Phenobarbital has been shown to reduce the response to thyroxine. Prescribers should be alert for changes in thyroid status if barbiturates are added or withdrawn from patients being treated for hypothyroidism. The effect of phenobarbital can be reduced by concomitant use of the herbal remedy St. John's wort (Hypericum perforatum). A marked increase in serious skin reactions has been seen in children given cefotaxime and phenobarbital. Phenobarbital may increase the risk of hypersensitivity reactions with the antineoplastic, procarbazine. Two cases of hepatotoxicity have been reported in patients on phenobarbital after taking paracetamol. Encephalopathy has been reported in a patient taking phenobarbital and the alkylating cytotoxic drug, ifosfamide. Interactions between antiepileptics are complex. C oncomitant administration of phenobarbital with other antiepileptics may enhance toxicity without a corresponding increase in antiepileptic effect. Interactions are usually caused by hepatic enzyme induction or hepatic enzyme inhibition. Oxcarbazepine, phenytoin and valproate often raise the plasma concentration of phenobarbital. As primadone is substantially converted into phenobarbital within the body elevated phenobarbital levels will arise if they are given concurrently. In contrast, vigabatrin sometimes lowers the plasma concentration of phenobarbital. 4.6 Pregnanc and lactation

The use of phenobarbital in pregnancy, especially the first and third trimesters should be avoided unless it is considered to be essential. Phenobarbital can cross the placental barrier and there is an increased risk of teratogenicity. Neonatal bleeding may occur and prophylactic treatment with vitamin k 1 for mother before delivery (as well as for the neonate) is recommended. Patients taking phenobarbital should be adequately supplemented with folic acid before conception and during pregnancy.
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Phenobarbital is excreted into breast milk and there is a small risk of neonatal sedation. Breast-feeding is therefore not advisable. 4.7 Effects on abilit to drive and use machines

May cause drowsiness. Phenobarbital may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery. If patients are affected they should not drive or operate machinery. 4.8 Undesirable effects The side effects of therapeutic doses are mild and include headache, insomnia, subtle mood changes, respiratory depression, sedation, drowsiness, lethargy, mental depression, allergic skin reactions maculopapular morbilliform or scarlatiniform rashes; fixed-drug eruptions and photosensitivity may occur. Severe reactions such as purpura exfoliative dermatitis, erythema multiforme and toxic epidermal necrolysis are extremely rare. Nystagmus and ataxia may occur with excessive doses. Paradoxical excitement, restlessness and confusion may occur in the elderly or in the presence of pain. Memory and cognitive impairment, hyperactivity and behavioural disturbance, irritability and hyperexcitability may occur in children. Megaloblastic anaemia (due to folate deficiency) has developed during chronic administration of phenobarbital for epilepsy and hypoprothrombinaemia has occurred in infants of mothers who have received phenobarbital during pregnancy. Hepatitis, cholestasis and osteomalacia have been associated with barbiturate administration. C ontinued use of phenobarbital, even in therapeutic doses, may result in psychic or physical dependence. Abrupt withdrawal of the drug may result in a severe abstinence syndrome which includes grand mal seizures and delirium; withdrawal should be cautious and gradual. Disturbances of liver function have been reported and there is some evidence that phenobarbital interferes with vitamin D metabolism. Rare effects include macrocytic anaemia, Dupuytren's contracture, Stevens-Johnson syndrome, hypocalcaemia, hypophosphataemia and metabolic bone disease in children on poor diets receiving long term phenobarbital. 4.9 Overdose The toxic effects of overdosage include drowsiness, prolonged coma, respiratory depression and cardiovascular depression, with hypotension and shock leading to renal failure. The duration and depth of cerebral depression varies with the dose and tolerance of the patient. Absent bowel sounds are a sign of severe poisoning. Hypothermia is common, with associated pyrexia during recovery. C haracteristic erythematous or haemorrhagic blisters occur in about 6% of patients. Death is usually due to respiratory and circulatory failure. The chronic effects of phenobarbital on neurological and psychic functions closely resemble those of alcohol. The symptoms of chronic poisoning include disorientation, mental confusion, ataxia, dizziness, depression and skin rashes. The aims in treating poisoning with phenobarbital are to maintain respiration, treat shock and prevent further absorption of the drug. Supportive measures alone may be sufficient if symptoms are mild. Analeptics should generally be avoided. However a single dose of nikethamide may be given in an emergency. If within 4 hours of ingestion, gastric aspiration or lavage may be of benefit in adults. The stomach should be emptied by lavage with warm water to leave the stomach empty, but only after precautions have been taken to avoid aspiration. Apomorphine induced emesis evacuates the stomach more rapidly and reliably than doses of ipecacuanha. After lavage, a saline cathartic should be administered and repeated every 1 to 2 hours, as long as bowel sounds are present. The prime objective of treatment is to maintain vital functions while the majority of the drug is metabolised by hepatic enzymes. Given normal renal function, forced alkaline diuresis (maintaining the urinary pH at approximately 8 by intravenous fusion) may enhance the excretion of the drug from the kidneys. The potentially fatal dose of phenobarbital is 6 to 10g. Attention should be paid to maintenance of a patient's airway and to the prevention of hypostatic pneumonia. Measures should be taken to prevent further loss of body heat. In severe acute intoxication circulatory collapse is a major threat. Dehydration is often severe. Hypovolemia must be corrected and if necessary the blood pressure can be supported with dopamine. Should renal failure occur, haemodialysis or charcoal haemoperfusion may be used to dispose of the poison. C harcoal haemoperfusion is the treatment of choice for the majority of patients with very severe barbiturate poisoning who fail to improve, or who deteriorate despite good supportive care.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacod namic properties The barbiturates reversibly depress the activity of all excitable tissues. Not all tissues are affected at the same dose or concentration and when barbiturates are given in sedative or hypnotic doses there is very little effect on skeletal, cardiac or smooth muscle.
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Phenobarbital Elixir BP - electronic Medicines Compendium (eMC) - print fri

Phenobarbital is a barbiturate drug which has selective anticonvulsant activity and is used to control tonicclonic seizures in the treatment of epilepsy. In a dose that has only minor effects on the reticular system, phenobarbital elevates the threshold for the initiation of afterdischarges, shortens the period of afterdischarge, and suppresses the spread of seizures. 5.2 Pharmacokinetic properties Oral absorption of phenobarbital is complete but slow, peak plasma concentrations occur several hours after a single dose. It is about 40% bound to plasma proteins and bound to a similar extent in tissues. The volume of distribution is approximately 0.9 lkg- 1 . About 25% of phenobarbital is eliminated by pH-dependent renal excretion, the remainder is inactivated by the hepatic microsomal enzymes. The major metabolite is the para hydroxyphenyl derivative, which is inactive and is excreted in the urine partly as the sulphate conjugate. Phenobarbital has a plasma half-life of up to about 75 hours in children and 100 hours in adults. This is increased in the elderly, in overdosage and in renal or hepatic disease. 5.3 Preclinical safet data

No data of relevance, which is additional to that included in other sections of the SPC

6. PHARMACEUTICAL PARTICULARS
6.1 List of e cipients Anise oil BP, coriander oil BP, ethanol (96%) BP, glycerol BP, orange oil terpeneless BP, lemon oil terpeneless BP, tartrazine solution compound BP, purified water BP. 6.2 Incompatibilities No major incompatibilities known. 6.3 Shelf life 500ml: 36 months unopened. 6.4 Special precautions for storage Store below 25 C Protect from light. 6.5 Nature and contents of container 500ml: amber glass bottle with plastic cap with EPE/Saranex liner or white plastic child resistant cap with EPE/Saranex liner. 6.6 Special precautions for disposal and other handling None.

7. MARKETING AUTHORISATION HOLDER

THORNTON & ROSS LTD HUDDERSFIELD HD7 5QH ENGLAND

8. MARKETING AUTHORISATION NUMBER(S)

PL 00240/6313R

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

27/5/82, 8/7/97

10. DATE OF REVISION OF THE TEXT

18/09/08
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Phenobarbital Elixir BP - electronic Medicines Compendium (eMC) - print fri

11 DOSIMETRY (IF APPLICABLE)

No Applicable

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)

No Applicable

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