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Meprobamate Tablets 400mg

Document: spc-doc_PL 17225-0003 change

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Meprobamate Tablets 400mg

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Meprobamate 400mg.

Meprobamate (INN, BAN) is chemically described as 2-Methyl-2-propyltrimethylene dicarbamate.

3. PHARMACEUTICAL FORM

Tablet.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

For the short-term treatment of anxiety states, muscle tension and associated conditions where anxiety is present.

4.2.    Posology and Method of Administration Posology

Adults. The recommended dose is 400mg three times daily, with an additional tablet before bed-time.

Elderly: May respond to lower doses, with half the normal adult dose or less may be sufficient.

Children. Not recommended.

Administration

For oral administration.

Contra-indications

4.3.


Use in patients known to be hypersensitive to the active ingredient or to related compounds such as carisprodol or carbromal.

Use in patients with a known propensity for dependence on drugs including alcohol.

Use in patients susceptible to attacks of acute intermittent porphyria.

Meprobamate should not be used during lactation. There is no evidence as to drug safety in human pregnancy, nor is there evidence that it is free from hazard. Meprobamate should not be used during pregnancy, especially during the first trimester, unless there are compelling reasons.

Acute pulmonary insufficiency.

Respiratory Depression.

4.4. Special Warnings and Special Precautions for Use

Patients should be advised that since their tolerance for alcohol and other central nervous depressants may be diminished in the presence of meprobamate, these substances should be avoided or taken in reduced dosage.

The concurrent use of other CNS depressant drugs should be avoided in hepatic or renal insufficiency.

Individual response in overdosage is variable, but in some cases the symptoms may be severe. It is therefore advisable that caution should be observed in prescribing meprobamate to patients with depression, or to others who may be liable to suicidal ideation or intent.

Use with caution in patients with respiratory disease or muscle weakness.

Meprobamate may induce seizures in epileptic patients, and meprobamate withdrawal may precipitate convulsions.

Some degree of dependence may occur in certain cases if dosage recommendations are exceeded. This is more likely in individuals with emotionally unstable personalities if the drug is taken over long periods, or in others liable to alcohol or other drug dependence. Withdrawal reactions have occurred ranging in severity from mild to severe. Severe reactions have been associated with high doses when the drug has been used over a prolonged period and withdrawn abruptly. Symptoms of tremulousness, insomnia, confusion, delirium tremens, and convulsions have

occurred. Very occasionally, fatalities have been recorded. When the drug has been withdrawn gradually, the withdrawal symptoms, if any, have usually been mild. It is advisable to monitor treatment regularly and to withdraw treatment gradually.

Safety and efficacy of meprobamate have not been established beyond short term use.

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

Like barbiturates, meprobamate can cause induction of liver enzymes, so that the availability and blood levels of drugs given concurrently that are metabolised in the liver may be affected. These include the following: coumarin-type anticoagulants, systemic steroids (including oral contraceptives), phenytoin, griseofulvin, rifampicin, phenothiazines (such as chlorpromazine) and tricyclic antidepressants. The clinical importance of enzyme induction by meprobamate on concurrently administered agents has not been established.

Meprobamate may increase the effects of concurrently administered central nervous system depressants.

Concomitant use of alcohol is not recommended. The sedative effects may be enhanced when meprobamate is used in combination with alcohol. This will affect the ability to drive or use machines.

4.6 Pregnancy and Lactation

There is no evidence as to drug safety in human pregnancy, nor is there evidence that it is free from hazard. Meprobamate diffuses across the placenta, and should not be used during pregnancy, especially during the first three months, unless there are compelling reasons, and the benefit to the mother is considered to outweigh any potential risks to the developing foetus.

Meprobamate appears in breast milk at concentrations up to four times those in maternal plasma, and may cause drowsiness in the infant. Meprobamate should not be used by patients who are breast-feeding.

4.7. Effects on Ability to Drive and Use Machines

This product may cause drowsiness or dizziness which may adversely affect the ability to drive or operate machinery.

4.8. Undesirable Effects

Drowsiness and dizziness may be experienced, but these symptoms usually disappear as treatment continues. Ataxia, hypotension, paraesthesia and paradoxical excitement may also occur.

Transient nausea has been reported. Other gastrointestinal symptoms include vomiting, stomatitis and proctitis.

Hypersensitivity reactions have been reported in about 2% of patients. These reactions include skin rashes, and may arise after one to four doses of the drug. They may be generalised or local, and may include urticaria, itchy maculopapular rashes or erythema. Severe systemic reactions with shaking, chills and fever, nausea and vomiting, hypotension and collapse have occasionally occurred.

Rarely reported reactions, usually occurring as a part of a generalised hypersensitivity reaction include anaphylaxis, hyperpyrexia, angioneurotic oedema, bronchospasm, oliguria and anuria.

Other reported dermatological reactions include erythema multiforme, exfoliative dermatitis, Stevens Johnson syndrome and bullous dermatitis.

Blood disorders including non-thrombocytopenic purpura, and rarely, thrombocytopenia, agranulocytosis, aplastic anaemia and pancytopenia have occurred.

Withdrawal symptoms may occur when meprobamate is discontinued abruptly after prolonged use (see Special Warnings and Precautions for Use).

4.9. Overdose

Acute poisoning with meprobamate produces coma, shock, vasomotor and respiratory collapse. Very few suicide attempts have proved successful and documented fatal doses have ranged from 12g to 47.6g. Recovery has occurred after ingestion of similar large amounts (20-40g). Gastric lavage is only effective within a short period of time as meprobamate is rapidly absorbed from the gastrointestinal tract. Blood concentrations may be reduced by a regimen of forced alkaline diuresis or haemodialysis. Respiration may require assistance.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Meprobamate is a carbamate with hypnotic, sedative and some muscle relaxant properties. In therapeutic doses its sedative effect rather than a direct action may be responsible for muscle relaxation.

5.2.


Pharmacokinetic Properties

Meprobamate is readily absorbed from the gastrointestinal tract ; peak plasma concentrations occur one to three hours after ingestion. Meprobamate is widely distributed.

It is extensively metabolised in the liver and is excreted in the urine mainly as an inactive hydroxylated metabolite and its glucuronide conjugate. About 10% of a dose is excreted unchanged.

The half-life is reported to range from six to seventeen hours, although this may be prolonged after chronic administration.

Meprobamate elimination may be prolonged in patients with chronic liver disease.

5.3. Pre-clinical Safety Data

None stated

6. PHARMACEUTICAL PARTICULARS

6.1.    List of Excipients

Polacrilin potassium, microcrystalline cellulose, methylcellulose, magnesium stearate.

6.2.    Incompatibilities

None.

6.3.    Shelf Life

60 months.

6.4.    Special Precautions for Storage

Store at room temperature, at or below 25°C.

6.5. Nature and Contents of Container

Amber glass bottle or white polypropylene securitainer containing 84 or 250 tablets.

6.6. Instructions for Use/Handling

None

7. MARKETING AUTHORISATION HOLDER

Genus Pharmaceuticals Holdings Limited

T/A Genus Pharmaceuticals

Park View House

65 London Road

Newbury

Berkshire

RG14 1JN

8 MARKETING AUTHORISATION NUMBER(S)

PL 17225/0003

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 12th September 1984

10 DATE OF REVISION OF THE TEXT

06/10/2008