SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

SECONAL SODIUM

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 100mg of Secobarbital Sodium

3.    PHARMACEUTICAL FORM

Capsule

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

For the short term treatment of severe, intractable insomnia in patients already taking barbiturates. New patients should not be started on this preparation. Attempts should be made to wean patients off this preparation by gradual reduction of the dose over a period of days or weeks (see drug abuse and dependence). Abrupt discontinuation should be avoided as this may precipitate withdrawal effects (see warnings).

4.2.    Posology and Method of Administration

For oral administration to adults only. Normal dosage is 100 mg at bedtime.

THE ELDERLY

Seconal Sodium is not recommended for use in elderly or debilitated patients.

CHILDREN

Seconal should not be administered to children or young adults.

In studies, Secobarbital sodium has been found to lose most of its effectiveness for both inducing and maintaining sleep by the end of two weeks of continued drug administration, even with the use of multiple doses.

Contraindications

Hypersensitivity to barbiturates, a history of manifest or latent porphyria, marked impairment of liver function or respiratory disease in which dyspnoea or obstruction is evident.

Barbiturates should not be administered to children, young adults, patients with a history of drug or alcohol addiction or abuse, the elderly and the debilitated.

4.4 Special warnings and precautions for use

Addiction potential: Secobarbital sodium may be habit forming. Tolerance and psychological and physical dependence may occur with continued use. Patients who have psychological dependence on barbiturates may increase the dosage or decrease the dosage interval without consulting a doctor and, subsequently, may develop a physical dependence on barbiturates.

To minimise the possibility of overdosage or development of dependence, the amount prescribed should be limited to that required for the interval until the next appointment.

Withdrawal symptoms occur after long term normal use (and particularly after abuse) on rapid cessation of barbiturate treatment. Symptoms include nightmares, irritability and insomnia and, in severe cases,tremors, delirium, convulsions and death.

Barbiturates should be withdrawn gradually from any patient known to be taking excessive doses over long periods.

Caution should be exercised when barbiturates are administered in the presence of acute or chronic pain, because paradoxical excitement could be induced or important symptoms could be masked.

Information for patients: The following information should be given to patients receiving Secobarbital:

The use of Secobarbital carries with it an associated risk of psychological and/or physical dependence. The patient should be warned against increasing the dose of the drug without consulting a doctor.

Secobarbital may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly.

Alcohol should not be consumed while taking Secobarbital. The concurrent use of Secobarbital with other CNS depressants (eg alcohol, narcotics, tranquillisers and antihistamines) may result in additional CNS depressant effects.

Drug abuse and dependence: Barbiturates may be habit forming; tolerance,psychological and physical dependence may occur especially following prolonged use of high doses. Daily administration in excess of 400 mg Secobarbital, for approximately 90 days, is likely to produce some degree of physical dependence.

A dosage of 600 - 800 mg, for at least 35 days, is sufficient to produce withdrawal seizures. The average daily dose for the barbiturate addict is usually about 1.5g.

As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than twofold. As this occurs, the margin between intoxicating dosage and fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is also ingested.

Symptoms of acute intoxication include unsteady gait, slurred speech and sustained nystagmus. Mental signs of chronic intoxication include confusion, poor judgement, irritability, insomnia and somatic complaints.

The symptoms of barbiturate withdrawal can be severe and may cause death. Minor withdrawal symptoms may appear 8 to 12 hours after the last dose of a barbiturate. These symptoms usually appear in the following order: anxiety, muscle twitching, tremor of hands and fingers, progressive weakness, dizziness, distortion in visual perception, nausea, vomiting, insomnia and orthostatic hypotension. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to five days after abrupt cessation of barbiturates. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Individuals susceptible to barbiturate abuse and dependence include alcoholics and opiate abusers, as well as other sedative-hypnotic and amphetamine abusers.

Dependence on barbiturates arises from repeated administration on a continuous basis, generally in amounts exceeding therapeutic dose levels. Treatment of dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of withdrawal regimens. In all cases, withdrawal takes an extended period. One method involves substituting a 30 mg dose of Phenobarbital for each 100 - 200 mg dose of barbiturate that the patient has been taking. The total daily amount of Phenobarbital is then administered in three or four divided doses, not to exceed 600 mg daily. Should signs of withdrawal occur on the first day of treatment, a loading dose of 100 to 200 mg of Phenobarbital may be administered intramuscularly in addition to the oral dose. After stabilisation on Phenobarbital, the total daily dose is decreased by 30 mg a day as long as withdrawal is proceeding smoothly. A modification of this regimen involves initiating treatment at the patient’s regular dosage level and decreasing the daily dosage by 10% as tolerated by the patient.

Infants that are physically dependent on barbiturates may be given Phenobarbital, 3 to 10 mg/kg/day. After withdrawal symptoms (hyperactivity, disturbed sleep, tremors and hyperreflexia) are relieved, the dosage of Phenobarbital should be gradually decreased and completely withdrawn over a two week period.

Carcinogenesis: Animal data show that Phenobarbital can be carcinogenic after lifetime administration.

Human data: In a 29 year epidemiological study of 9136 patients who were treated on an anticonvulsant protocol that included Phenobarbital, results indicated a higher than normal incidence of hepatic carcinoma. Previously some of these patients had been treated with thorotrast, a drug that is known to produce hepatic carcinomas. Thus, this study did not provide sufficient evidence that Phenobarbital is carcinogenic in humans.

A retrospective study of 84 children with brain tumours, matched to 73 normal controls and 78 cancer controls (malignant disease other than brain tumours), suggested an association between exposure to barbiturates prenatally and an increased incidence of brain tumours.

Barbiturates should be administered with caution, if at all, to patients who are mentally depressed or have suicidal tendencies. They should also be used with great caution and at reduced dosage in those with hepatic disease, marked renal dysfunction, shock or respiratory depression.

Elderly or debilitated patients may react to barbiturates with marked excitement, depression or confusion (see ‘Contra-indications’). In some persons, barbiturates repeatedly produce excitement rather than depression.

Barbiturates should not be administered to patients showing the premonitory signs of hepatic coma (see ‘Contra-indications’).

A cumulative effect may occur with the barbiturates leading to features of chronic poisoning including headache, depression and slurred speech.

Automatism may follow the use of a hypnotic dose of barbiturate

Laboratory tests: Prolonged therapy with barbiturates should be accompanied by periodic evaluation of, for examplethe haematopoietic, renal and hepatic systems (but see ‘Uses).

4.5. Interactions with other Medicinal Products and other forms of Interaction

Toxic effects and fatalities have occurred following overdoses of Secobarbital alone and in combination with other CNS depressants. Caution should be exercised in prescribing unnecessarily large amounts of Secobarbital for patients who have a history of emotional disturbances or suicidal ideation or who have misused alcohol or other CNS drugs.

Anticoagulants, Antivirals, Calcium-channel Blockers, Ciclosporin, Levothyroxine, Theophylline : Barbiturates cause induction of the liver microsomal enzymes responsible for metabolising many other drugs. In particular they may result in increased metabolism, reduced plasma concentrations and decreased clinical response to: Oral anticoagulants (eg warfarin); antivirals (eg indinavir, nelfinavir, saquinavir); calcium-channel blockers (eg diltiazem, felodipine, isradipine, nicardipine, nifedipine, verapamil); ciclosporin; levothyroxine (thyroxine); theophylline. Patients stabilised on any of these therapies may require dosage adjustments if barbiturates are added to, or withdrawn from, their regimen.

Corticosteroids: Barbiturates appear to enhance the metabolism of exogenous corticosteroids and steroid dosage may also need adjustment.

Griseofulvin: Barbiturates may interfere with the absorption of oral griseofulvin, thus decreasing its blood level. Concomitant administration should be avoided if possible.

Doxycycline: Barbiturates may shorten the half-life of doxycycline for as long as two weeks after the barbiturate is discontinued. If administered concomitantly the clinical response to doxycycline should be monitored closely.

Phenytoin, Sodium Valproate, Valproic Acid: The effect of barbiturates on phenytoin metabolism is variable. Phenytoin and barbiturate blood levels should be monitored more frequently if administered concomitantly. Sodium valproate and valproic acid increase Secobarbital serum levels. Therefore these levels should be monitored and dosage adjustments made as clinically indicated.

CNS Depressants: Concomitant use of other CNS depressants, including other sedatives or hypnotics, antihistamines, tranquillisers or alcohol, may produce additive depressant effects.

Monoamine Oxidase Inhibitors (MAOIS): Prolong the effects of barbiturates.

Oestradiol, oestrone, progesterone and other steroidal hormones: There have been reports of patients treated with antiepileptic drugs (eg Phenobarbital) who became pregnant while taking oral contraceptives. Barbiturates may decrease the effect of oestradiol. An alternative contraceptive method might be suggested to women taking barbiturates.

Pregnancy and Lactation

Usage in Pregnancy: Barbiturates are contraindicated during pregnancy since they can cause foetal harm. A higher than expected incidence of foetal abnormalities may be connected with maternal consumption of barbiturates. Barbiturates readily cross the placental barrier and are distributed throughout foetal tissues with highest concentrations in placenta, foetal liver and brain. Withdrawal symptoms occur in infants born to women who receive barbiturates during the last trimester of pregnancy. If a patient becomes pregnant whilst taking this drug, she should be told of the potential hazard to the foetus.

Reports of infants suffering from long term barbiturate exposure in utero included the acute withdrawal syndrome of seizures and hyper-irritability from birth to a delayed onset of up to 14 days.

Labour and Delivery: Respiratory depression has been noted in infants born following the use of barbiturates during labour. Premature infants are particularly susceptible. Resuscitation equipment should be available.

Nursing Mothers: Small amounts of barbiturates are excreted in the milk and they are therefore contraindicated for the nursing mother.

4.7. Effects on Ability to Drive and Use Machines

Secobarbital may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient should be cautioned accordingly

4.8. Undesirable Effects

The following adverse reactions and their incidences were compiled from surveillance of thousands of hospitalised patients who received barbiturates. As such patients may be less aware of certain of the milder adverse effects of barbiturates, the incidence of these reactions may be somewhat higher in fully ambulatory patients.

More than 1 in 100patients: The most common adverse reaction, estimated to occur at a rate of 1 to 3 patients per 100, is the following:

NERVOUS SYSTEM: Somnolence

LESS THAN 1 IN 100 PATIENTS: Adverse reactions estimated to occur at a rate of less than 1 in 100 patients are listed below grouped by organ system and by decreasing frequency:

NEUROLOGICAL: Agitation, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia, anxiety, dizziness, abnormal thinking.

RESPIRATORY: Hypoventilation, apnoea.

CARDIOVASCULAR: Bradycardia, hypotension, syncope.

DIGESTIVE: Nausea, vomiting, constipation

OTHER: Headache, hypersensitivity reactions (angioneurotic oedema, rashes, exfoliative dermatitis), fever, liver damage. Hypersensitivity is more likely to occur in patients with asthma, urticaria or angioneurotic oedema. Megaloblastic anaemia has followed chronic Phenobarbital use.

4.9. Overdose

The toxic dose of barbiturates varies considerably. In general, an oral dose of 1g of most barbiturates produces serious poisoning in an adult. Death commonly occurs after 2 to 10g of ingested barbiturate. The sedative, therapeutic blood levels of Secobarbital range between 0.5 and 5 mg/l; the usual lethal blood level ranges from 15 to 40 mg/l. Barbiturate intoxication may be confused with alcoholism, bromide intoxication and various neurological disorders. Potential tolerance must be considered when evaluating significance of dose and plasma concentration.

In extreme overdose, all electrical activity in the brain may cease, in which case a “flat” EEG normally equated with clinical death cannot be accepted. This effect is fully reversible unless hypoxic damage occurs. Consideration should be given to the possibility of barbiturate intoxication even in situations that appear to involve trauma.

SIGNS AND SYMPTOMS: Symptoms of oral overdose may occur within 15 minutes and begin with CNS depression, absent or sluggish reflexes, underventilation, hypotension and hypothermia, which may progress to pulmonary oedema and death. Haemorrhagic blisters may develop, especially at pressure points.

Complications such as pneumonia, pulmonary oedema, cardiac arrhythmias, congestive heart failure and renal failure may occur. Uraemia may increase CNS sensitivity to barbiturates if renal function is impaired. Differential diagnosis should include hypoglycaemia, head trauma, cerebrovascular accidents, convulsive states and diabetic coma.

TREATMENT OF OVERDOSAGE

General management should consist of symptomatic and supportive therapy. Activated

charcoal may be more effective than emesis or lavage. Diuresis and peritoneal dialysis are of little value. Haemodialysis and haemoperfusion enhance drug clearance and should be considered in serious poisoning. If the patient has chronically abused sedatives, withdrawal reactions may be manifest following acute overdose.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Seconal Sodium (Secobarbital sodium), a short acting barbiturate, is a CNS depressant. In ordinary doses the drug acts as a sedative and hypnotic.

Barbiturates are capable of producing all levels of CNS mood alteration, from excitation to mild sedation, hypnosis and deep coma. Overdosage can product death. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function and produce drowsiness, sedation and hypnosis.

Barbiturate-induced sleep differs from physiologic sleep. Sleep laboratory studies have demonstrated that barbiturates reduce the amount of time spent in the rapid eye movement (REM) phase of sleep, or dreaming stage. Also stages III and IV sleep are decreased. Following abrupt cessation of barbiturates used regularly, patients may experience markedly increased dreaming, nightmares and/or insomnia. Therefore, withdrawal of a single therapeutic dose over five or six days has been recommended to lessen the REM rebound and disturbed sleep which contribute to drug withdrawal syndrome (for example, decrease the dose from 3 to 2 doses a day for 1 week).

5.2. Pharmacokinetic Properties

Barbiturates are weak acids that are absorbed and rapidly distributed to all tissues and fluids, with high concentrations in the brain, liver and kidneys. Lipid solubility of the barbiturates is the dominant factor in their distribution within the body. Barbiturates are bound to plasma and tissue proteins; the degree of binding increases as a function of lipid solubility. The onset of action of Seconal Sodium is from 10 to 15 minutes and the duration of action ranges from 3 to 4 hours. The plasma half life of Seconal Sodium is 15 - 40 hours.

Secobarbital sodium has a high lipid solubility, plasma protein binding, brain protein binding, a short delay in onset of activity and a short duration of action.

Seconal is metabolised primarily by the hepatic microsomal enzyme system and the metabolic products are excreted in the urine and, less commonly, in the faeces. Seconal is detoxified in the liver.

5.3. Preclinical Safety Data

Carcinogenesis: Animal data show that phenobarbital can be carcinogenic after lifetime administration.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Starch, Silicone, Erythrosine, Quinoline yellow, Gelatin, Black Iron Oxide, Shellac

6.2.    Incompatibilities

Not applicable.

6.3.    Shelf Life

60 months.

6.4.    Special Precautions for Storage

Store below 25°C. Keep lid tightly closed.

6.5.    Nature and Contents of Container

High density polyethylene bottles with screw caps containing 100 capsules.

6.6. Instruction for Use/Handling

Not applicable.

7. MARKETING AUTHORISATION HOLDER

Flynn Pharma Ltd.

Alton House,

4 Herbert Street Dublin 2,

Republic of Ireland

8. MARKETING AUTHORIZATION NUMBER(S)

PL 13621/0003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/12/2008

10 DATE OF REVISION OF THE TEXT

12/12/2008