Clonzy 2

Clonazepam shares the pharmacological properties common to benzodiazepines, including anticonvulsant, sedative, muscle-relaxing and anxiolytic effects. The central actions of benzodiazepines come from a strengthening of GABAergic neurotransmission at inhibitory synapses. In the presence of benzodiazepines, the GABA receptor's affinity for the neurotransmitter is heightened through positive allosteric modulation, resulting in a greater action of released GABA on the postsynaptic transmembrane chloride ion flux. There are also animal data showing an effect of clonazepam on serotonin. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity, including the spike-and-wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves. Generalized EEG abnormalities are more consistently suppressed than focal abnormalities. Based on these findings, clonazepam has beneficial effects in both generalized and focal epilepsies.

Pregnancy: Animal studies can't rule out that clonazepam may cause congenital malformations. Epidemiological evaluations suggest that anticonvulsant drugs act as teratogens. But the published reports make it hard to say which drug, or which combination of drugs, is responsible for defects in the newborn. Other factors, such as genetic factors or the epileptic condition itself, may matter more than the drug treatment in causing birth defects. So clonazepam should be given to a pregnant woman only if the potential benefit outweighs the risk to the foetus. During pregnancy it may be given only when there is a compelling indication.

High doses in the last trimester of pregnancy or during labour can cause irregular heartbeat in the unborn child. In the neonate they can cause hypothermia, hypotonia, mild respiratory depression and poor feeding. Pregnancy itself, and also abrupt stopping of the medicine, can make epilepsy worse, and this should be kept in view. Withdrawal symptoms in newborn infants have occasionally been reported with benzodiazepines.

Nursing Mothers: The active ingredient of clonazepam passes into breast milk in small amounts only. Even so, mothers being treated with this drug should not breastfeed. If there is a compelling indication for clonazepam, breastfeeding should be stopped.

Pediatric Use: In infants and small children, Clonazepam may increase the production of saliva and bronchial secretion. Because of this, special attention must be paid to keeping the airways open. Geriatric Use: Benzodiazepines seem to act more strongly in elderly patients than in younger ones, even when plasma benzodiazepine concentrations are similar. This may be due to age-related changes in drug and receptor interactions, post-receptor mechanisms and organ function. Renal Impairment: Renal impairment does not affect the pharmacokinetics of Clonazepam, so on pharmacokinetic grounds no dose adjustment is required in these patients. Hepatic Impairment: Plasma protein binding of Clonazepam in cirrhotic patients is significantly different from that in healthy subjects (free fraction 17.1±1.0% vs 13.9±0.2%). The influence of hepatic impairment on Clonazepam pharmacokinetics has not been investigated further. However, experience with nitrazepam, a closely related nitrobenzodiazepine, indicates that the clearance of unbound Clonazepam might be reduced in liver cirrhosis.

Symptoms: Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. An overdose of Clonazepam is seldom life-threatening if the drug is taken alone, but it may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and coma. If coma occurs, it usually lasts a few hours, though it can be longer and cyclical, particularly in elderly patients. Seizures may become more frequent in patients whose plasma concentrations are supratherapeutic. The respiratory depressant effects of benzodiazepines are more serious in patients with respiratory disease. Benzodiazepines also increase the effects of other central nervous system depressants, including alcohol.

Treatment: Monitor the patient's vital signs and start supportive measures according to the patient's clinical state. In particular, patients may need symptomatic treatment for cardiorespiratory or central nervous system effects. Further absorption should be prevented by an appropriate method, for example activated charcoal given within 1 to 2 hours. If activated charcoal is used, protecting the airway is imperative for drowsy patients. Where several substances have been taken together, gastric lavage may be considered, but not as a routine measure. If CNS depression is severe, consider flumazenil, a benzodiazepine antagonist. It should only be given under closely monitored conditions. Its half-life is short (about an hour), so patients given flumazenil need monitoring after its effects have worn off. Use flumazenil with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). For further information on the correct use of Clonazepam, refer to the prescribing information for flumazenil.

Store Clonazepam in a dry place, away from light and heat. Keep it out of the reach of children.