KRATIUM Tablet Ref.[27828] Active ingredients: Diazepam

Diazepam should be avoided in patients with pre-existing CNS depression or coma, respiratory depression, acute pulmonary insufficiency, or sleep apnoea, and used with care in those with chronic pulmonary insufficiency. Diazepam should be given with care to elderly or debilitated patients who may be more prone to adverse effects.

Caution is required in patients with muscle weakness, or impaired liver or kidney function; its use should be avoided in severe hepatic impairment. The sedative effects of diazepam are most marked during the first few days of administration;affected patients should not drive or operate machinery (see also Driving, Monitoring of cardio respiratory function is generally recommended when benzodiazepines are used for deep sedation.

Diazepam is not appropriate for the treatment of chronic psychosis or for phobic or obsessional states. Diazepam-induced disinhibition may precipitate suicide or aggressive behaviour and it should not, therefore, be used alone to treat depression or anxiety associated with depression; it should also be used with care in patients with personality disorders. Caution is required in patients with organic brain changes particularly arteriosclerosis. In cases of bereavement, psychological adjustment may be inhibited by diazepam.

Dependence characterised by a withdrawal syndrome may develop after regular use of diazepam, even in therapeutic doses for short periods; because of its dependence liability, diazepam should be used with caution in patients with a history of alcohol or drug addiction.

Enhanced sedation or respiratory and cardiovascular depression may occur if diazepam or other benzodiazepines are given with other drugs that have CNS-depressant properties; these include alcohol, antidepressants, antihistamines, antipsychotics, general anaesthetics, other hypnotics or sedatives, and opioid analgesics. The sedative effect of benzodiazepines may also be enhanced by cisapride. Adverse effects may also be produced by concomitant administration with drugs which interfere with the metabolism of benzodiazepines. Drugs which have been reported to alter the pharmacokinetics of benzodiazepines are discussed in detail below but few of these interactions are likely to be of clinical significance. Benzodiazepines such as diazepam which are metabolised primarily by hepatic microsomal oxidation may be more susceptible to pharmacokinetic changes than those eliminated primarily by glucuronide conjugation.

Pregnancy

An increased risk of congenital malformations associated with the use of minor tranquilizers (diazepam, meprobamate and chlordiazepoxide) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.

Nursing mothers

Diazepam is known to be excreted in human milk. Chronic administration of benzodiazepines to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. As a general rule, benzodiazepines should not be given to lactating mothers.

Most benzodiazepines can adversely affect parameters of driving performance in healthy subjects. Patients affected by drowsiness while taking benzodiazepines should not drive or operate machinery. Drowsiness often becomes less troublesome with continued use of these drugs.

Drowsiness, sedation, muscle weakness, and ataxia are the most frequent adverse effects of diazepam use. They generally decrease on continued administration and are a consequence of CNS depression. Less frequent effects include vertigo, headache, confusion, depression, slurred speech or dysarthria, changes in libido, tremor, visual disturbances, urinary retention or incontinence, gastrointestinal disturbances, changes in salivation, and amnesia. Some patients may experience a paradoxical excitation which may lead to hostility, aggression, and disinhibition. Jaundice, blood disorders, and hypersensitivity reactions have been reported rarely. Respiratory depression and hypotension occasionally occur with high dosage and parenteral administration.

Pain and thrombophlebitis may occur with some intravenous formulations of diazepam; raised liver enzyme values have occurred.

Overdosage can produce CNS depression and coma or paradoxical excitation. However, fatalities are rare when taken alone.

Use of diazepam in the first trimester of pregnancy has occasionally been associated with congenital malformations in the infant but no clear relationship has been established. Administration of diazepam in late pregnancy has been associated with intoxication of the neonate.

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of diazepam. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (eg, dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

None reported.