hronic benzodiazepines may also be associated with atemporary increase in the frequency and/or severity of seizures.
10 OVERDOSAGE
Symptoms
The manifestations of midazolam overdosage reported are similar to those observed withother benzodiazepines, including sedation, somnolence, confusion, impaired coordination,diminished reflexes, coma, and untoward effects on vital signs.
Treatment
Treatment of midazolam overdosage is the same as that followed for overdosage with otherbenzodiazepines. Respiration, pulse rate, and blood pressure should be monitored and generalsupportive measures should be employed. Attention should be given to the maintenance of apatent airway and support of ventilation, including administration of oxygen. An intravenousinfusion should be started. Should hypotension develop, treatment may include intravenousfluid therapy, repositioning, judicious use of vasopressors appropriate to the clinical situation,
if indicated, and other appropriate countermeasures. There is no information as to whetherperitoneal dialysis, forced diuresis, or hemodialysis are of any value in the treatment ofmidazolam overdosage.
Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete orpartial reversal of the sedative effects of benzodiazepines and may be used in situations whenan overdose with NAYZILAM is known or suspected. There are anecdotal reports of adversehemodynamic responses associated with midazolam following administration of flumazenilto pediatric patients.
Prior to the administration of flumazenil, necessary measures should beinstituted to secure the airway, assure adequate ventilation, and establish adequate
intravenous access. The reversal of benzodiazepine effects may be associated with the onsetof seizures in certain high-risk patients. The prescriber should be aware of a risk of seizure inassociation with flumazenil treatment, particularly in long-term benzodiazepine users. Theadministration of flumazenil in cases of benzodiazepine overdose can lead to withdrawal andadverse reactions, including increased seizures. Its use in patients with epilepsy is typicallynot recommended.
11 DESCRIPTION
NAYZILAM contains midazolam, a compound of the benzodiazepine class. Midazolam ischemically designated as 8-Chloro-6-(ο-fluorophenyl)-1-methyl-4H-imidazo[1,5-
a][1,4]benzodiazepine, and it has the following structure:The empirical formula is C18H13ClFN3 representing a molecular weight of 325.8. Midazolam,
USP is a white or yellowish, crystalline powder that is practically insoluble in water, solublein methanol, and freely soluble in acetone and in alcohol.
NAYZILAM nasal spray is a clear, colorless to yellowish colored liquid. Each single-doseNAYZILAM unit is for nasal administration and delivers 5 mg of midazolam in 0.1 mL ofsolution containing ethanol; PEG-6 methyl ether; polyethylene glycol 400; propylene glycol;and purified water.
The pH range of solution is approximately 5.0 to 9.0.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The exact mechanism of action for midazolam is not fully understood, but it is thought toinvolve potentiation of GABAergic neurotransmission resulting from binding at thebenzodiazepine site of the GABAA receptor.
12.2 Pharmacodynamics
The pharmacodynamic properties of midazolam and its metabolites, are similar to those ofother benzodiazepines, including sedative, anx |
