Prazepam

Benzodiazepines, including prazepam, produce additive CNS depressant effects, including respiratory depression, when co-administered with other CNS depressants such as opioids, antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines.

In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychological dependence.

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required.

CYP3A4 inhibitors may reduce the metabolism of prazepam and increase the potential for toxicity.

Concomitant intake with alcohol is not recommended. The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.

Oral contraceptives can increase the effects of prazepam because oral contraceptives inhibit oxidative metabolism, thereby increasing serum concentrations of concomitantly administered benzodiazepines that undergo oxidation. Patients receiving oral contraceptive therapy should be observed for evidence of increased effects of prazepam. Caution is therefore recommended when oral contraceptives are co-administered with prazepam.

Studies in rats have shown a decrease in fertility and mating at high doses.

Benzodiazepines should be combined cautiously with clozapine because they could cause additive CNS depressant effects. Severe confusion, hypotension and respiratory depression have occurred rarely in those patients receiving clozapine concurrently or following benzodiazepine therapy. In patients receiving concomitant clozapine, the starting doses of the benzodiazepine should be approximately one-half of the usual dose until experience with the patient has been gained.

Alcohol, as well as disulfiram and cimetidine, significantly prolong the duration of action of prazepam.

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.

A lower dose is recommended for patients with chronic respiratory insufficiency, due to the risk of respiratory depression.

Benzodiazepines are not recommended for the primary treatment of psychotic illness.

There is no evidence regarding prazepam’s safety in human pregnancy, nor is there evidence from animal work that it is free from hazard. Animal studies with benzodiazepines have shown minor effects on the foetus while a few studies have reported late behavioural disturbances in offspring exposed in utero.

No adequate well-controlled, studies with prazepam have been performed in pregnant women. The data concerning teratogenicity associated with benzodiazepine exposure in humans are inconsistent. There are indications from some early studies that in utero exposure may be associated with congenital malformations. Later studies have provided no clear evidence of the association of benzodiazepine use and the development of these defects. In cases where an association with benzodiazepines was found, the exposure occurred mainly during the first trimester. Chronic administration during the last trimester may be associated with intrauterine growth retardation. Use during the last trimester up to delivery is associated with neonatal complications including respiratory distress syndrome, floppy infant syndrome (hypotonia, lethargy and sucking difficulties), and withdrawal syndrome (tremors, irritability, hypertonicity, diarrhea/vomiting and vigorous sucking). If benzodiazepines are used during pregnancy, or if the patient becomes pregnant while taking benzodiazepines, the patient should be apprised of the potential hazard to the fetus.

Studies with animals have shown reproductive toxicity.

Prazepam is not recommended during pregnancy and in women of childbearing potential not using contraception.

Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

In view of their molecular size, prazepam and its metabolites are probably excreted in human milk, therefore prazepam should not be given to nursing mothers.

Fertility

Studies in rats have shown a decrease in fertility and mating at high doses.

Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased.

The following side effects have been observed and reported. These findings are characteristic of benzodiazepine drugs with the following frequencies

^* Drowsiness during the day

Other side effects include the following:

Amnesia

Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour.

Depression

Pre-existing depression may be unmasked during benzodiazepine use.

Psychiatric and ‘paradoxical’ reactions

Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepine or benzodiazepine-like agents. They may be quite severe with this product. They aremore likely to occur in children and the elderly.

Dependence

Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena. Psychic dependence mayoccur. Abuse of benzodiazepines has been reported.