Description

Paxum is a psychotherapeutic agent of the most popular and widely used benzodiazepine derivative, diazepam. In many individuals, it produces satisfactory anxiolytic effect in doses that do not cause clinically important sedation or impairment of psychomotor function. Other than its use as an anxiolytic agent, diazepam is also used as an anticonvulsant and a sedative and skeletal muscle relaxant. In addition to these therapeutic actions the drug lacks significant side effects outside of Central Nervous System and has low toxicityÑthe factors that have contributed to its wide-spread clinical use.

Actions

Paxum (Diazepam) is presumed to act on the parts of the limbic system, thalamus and hypothalamus producing a state of calmness and has no demonstrable blocking action on the peripheral autonomic nervous system. Although the exact mechanisms of action are not fully understood, several processes are believed to be involved to exert their therapeutic effects. Part of the mechanisms of action of Paxum may be explained by its interaction with gamma aminobutyric acid (GABA) in the brain. The drug appears to facilitate synaptic GABA-ergic inhibitory mechanisms. It is also suggested that

(a)  in some cells, can induce their own forms of inhibition directly by producing an effect much like that evoked by GABA,

(b) the drug can also inhibit the release of neurotransmitters and

(c) an effect that might involve potentiation of GABA actions at presynaptic sites.

Paxum is rapidly absorbed after oral ingestion and peak plasma levels are reached in about an hour in adults and in 15 to 30 minutes in children. The effect is more rapid after i.v. administration; i.m. administration, however, produces lower peak plasma level than oral or i.v. administrations. Like other benzodiazepine derivatives diazepam is highly lipid soluble, widely distributed in the body tissues and is highly bound to plasma protein.

Both the gastrointestinal and cardiovascular systems are well known to be affected by stress, anxiety and autonomic activity and Paxum is reported to offer significant beneficial effects in regard of both psychic and somatic clusters. I.V. Paxum is used to produce sedation in psychiatric emergencies and in the treatment of drug induced systemic reactions, status epilepticus, tetanus and as an anaesthetic agent.

Indications

Paxum(Tablets & Injection) is useful in the treatment of anxiety disorders or for the short term relief of symptoms of anxiety.
Muscle relaxant-for the relief of muscle spasm due to inflammation of muscles, joints or secondary to trauma; spasticity caused by cerebral palsy, paraplegia; stiffman syndrome.  Also useful in the management of tetanus.
AnticonvulsantÑuseful as an adjunct in status epilepticus and in severe convulsive seizures.
Acute alcohol withdrawal-useful in the management of acute agitation, tremor, acute delirium tremens and hallucinosis.
Paxum is useful in premedication for the relief of anxiety and tension in patients undergoing surgical procedures; as an intravenous anaesthetic agent for brief operative procedures such as electric cardioversion, endoscopic procedures, dental surgery, reductions of minor fractures etc. As adjunctive therapy in labour, heatstroke, peptic ulcer and nausea vomiting

Contraindications

Hypersensitivity to benzodiazepines; psychosis; narrow angle glaucoma, oral use in children under 6 months of age.

Adverse Reactions

The side effects are usually mild and infrequent. Drowsiness, lightheadedness, ataxia have been reported especially in the elderly and debilitated patients.

Other effects less frequently reported include :
Central Nervous System-sedation, depression, lethargy, nervousness; Gastrointestinal System-constipation, dry mouth, change in appetite. Genitourinary System-incontinence, changes in libido, menstrual irregularities;
Cardiovascular System-bradycardia, tachycardia, hypotension, palpitation;
Paradoxical reactions such as acute hyperexcited status, insomnia, anxiety, increased muscle spasticity have been reported. Should these occur, the drug be discontinued

Precautions

Suicidal tendencies may be present in those patients with accompanying degree of depression and least amount of drug feasible should be administered.

In elderly or debilitated patients and in children initial dosage should be small and increments made gradually. Patients on prolonged therapy should have periodic blood counts and liver function tests. Alcohol may alter the patients response to diazepam. Diazepam readily crosses the placenta and due care should be taken in using it in late pregnancy. I.V. administration should be done slowly to avoid the risk of apnoea. Withdrawal of the drug from patients receiving very high doses or for prolonged period of time should be gradual. The drug should not be mixed with i.v. fluids or solutions of other drugs. Safety and efficacy of parenteral diazepam has not been established in the neonates.  

Drug Interactions

Concurrent use of Paxum (Diazepam) with
alcohol, narcotic analgesics, sedative-hypnotics leads to increased detrimental effect on psychomotor skills, hypotension and muscular weakness.

With Cimetidine the effects of diazepam may be enhanced leading to development of side effects; with antacids (aluminium hydroxide) the absorption of diazepam may be delayed.

Dosage & Administration

I.  Adults :      

    (a)  Tension/anxiety/psychoneurotic states :
  2 to 10 mg twice or thrice daily orally.

    (b)  Acute tension/anxiety/hallucinatory states :
10 to 20 mg thrice daily orally or 5 to 10 mg slow i.v. initially, which may be repeated
4 hours later, if necessary.

    (c)  Insomnia :
  5 to 30 mg orally at bedtime.

    (d)  Nervous exhaustion :
  5 mg at bedtime and 2.5 mg once or twice during the day orally.     

  (e)     Muscle spasms :
10 to 30 mg daily orally or 5 to 10 mg i.m. or i.v. initially, which may be repeated, if necessary, 4 hours later.

  (f)   Pre-operative medication : 
5 to 30 mg can be given orally before operation, or 10 mg i.m. or i.v. before surgery.

  (g)     Endoscopic procedures :
10 to 15 mg i.v. slowly just before the procedure.

(h)      As adjunctive therapy for cardioversion :
  5 to 15 mg i.v. 5-10 minutes before the procedure.

(i)     Management of acute alcohol withdrawal symptoms :
10 mg 3 or 4 times within first 24 hours followed by 5 mg thrice daily orally; or 10 mg i.m. or i.v. initially and if necessary may be repeated, 5 to 10 mg 4 hours later.

  (j)   In labour :
10 to 20 mg to be administered after 2 to 3 fingers dilatation of the cervix.

    (k)  As adjunctive therapy in convulsive disorders :  
  2.5 to 10 mg orally 2 to 4 times daily.

    (l)   Status epilepticus/severe recurrent convulsive seizures :
10 mg i.v. slowly every 15 minutes upto 30 mg. If necessary may be repeated 2-4 hours later.

    (m)     Management of tetanus :
  10 to 20 mg through i.v. route; can be repeated as required.

  II. Elderly and debilitated patients

          Starting doseÑ2.5 mg once or twice daily; to be increased gradually as desired.

III. Children

    (a)  Muscle spasms (above 6 months)

          2.5 to 10 mg daily orally.

    (b)     Convulsive disorders (above 6 months)

          2.5 to 10 mg daily orally.

    (c)  Tetanus (as adjunctive therapy)

          a)  below 5 years: 1 to 2 mg. i.m. or i.v. slowly, may be repeated 4 hours later, if necessary.

          b)  above 5 years: 5 to 10 mg i.m. or i.v. slowly, may be repeated 4 hours later, if necessary.

    (d)  Status epilepticus :

          a)  below 5 years: 0.25 to 0.5 mg. i.m. or i.v. slowly every 5 minutes upto 5 mg; may be repeated 4 hours later, if necessary.             b)          above 5 years : 1 mg. i.m. or i.v. slowly every 5 minutes upto 10 mg; if necessary, may be repeated 4 hours later.

N.B. Tablets not recommended for children below 6 months and injection not recommended below 30 days of age.

Packing

Paxum Tablets :
Strips of 10 tablets

Paxum Injection :
6 x 2 ml ampoules in a carton