DIAZEMULS Emulsion Ref.[2739] Active ingredients: Diazepam

Posology

Sedation

0.1-0.2mg diazepam/kg body weight by iv injection. The normal adult dose is 10-20 mg, but dosage should be titrated to the patient’s response.

Premedication

0.1-0.2mg diazepam/kg body weight by iv injection. Dosage should be titrated to the patient’s response. In this indication, prior treatment with diazepam leads to a reduction in fasciculations and postoperative myalgia associated with the use of suxamethonium.

Tetanus

0.1-0.3mg diazepam/kg body weight by iv injection repeated every 1-4 hours as required. Alternatively, continuous infusion of 3-10mg/kg body weight over 24 hours may be infused.

Status epilepticus

An initial dose 0.15-0.25mg/kg body weight by iv injection repeated in 30 to 60 minutes if required, and followed if necessary by infusion (see below) of up to 3mg/kg body weight over 24 hours.

Anxiety and tension, acute muscle spasm, acute states of excitation, delirium tremens

The usual dose is 10mg repeated at intervals of 4 hours, or as required.

Elderly or debilitated patients

Elderly and debilitated patients are particularly sensitive to benzodiazepines. Dosage should initially be reduced to one half of the normal recommendations.

Method of administration

Diazemuls may be administered by slow intravenous injection (1ml per min), or by continuous infusion. Diazemuls should be drawn into the syringe immediately prior to administration.

Mix well before use.

If a continuous infusion is required, Diazemuls can be added to dextrose solution 5% or 10% to achieve a final diazepam concentration within the range 0.1-0.4mg/ml (i.e. 2-8ml Diazemuls per 100ml dextrose solution). A dextrose solution containing Diazemuls should be used within 6 hours of the admixture. Diazemuls can be mixed in all proportions with intralipid 10% or 20% but not with saline solutions. It can be injected into the infusion tube during an ongoing infusion of isotonic saline or dextrose solution 5% or 10%. As with other diazepam injections, adsorption may occur to plastic infusion equipment. This adsorption may occur to a lesser degree with Diazemuls than with aqueous diazepam injection preparations when mixed with dextrose solutions.

Symptoms

The symptoms of diazepam overdose are mainly an intensification of the therapeutic effects (ataxia, drowsiness, dysarthria, sedation, muscle weakness, profound sleep, hypotension, bradycardia, nystagmus) or paradoxical excitation. In most cases only observation of vital functions is required.

Extreme overdosage may lead to coma, areflexia, cardiorespiratory depression and apnoea, requiring appropriate countermeasures (ventilation, cardiovascular support). Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease. Severe effects in overdose also include rhabdomyolysis and hypothermia.

Management

Maintain a clear airway and adequate ventilation.

Monitoring level of consciousness, respiratory rate, pulse oximetry and blood pressure in symptomatic patients.

Consider arterial blood gas analysis in patients who have a reduced level of consciousness (GCS <8; AVPU scale P or U) or have reduced oxygen saturations on pulse oximetry.

Correct hypotension by raising the foot of the bed and by giving an appropriate fluid challenge. Where hypotension is thought mainly due to decreased systemic vascular resistance, drugs with alpha-adrenergic activity such as noradrenaline or high dose dopamine (10-30 micrograms/kg/min) may be beneficial. The dose of inotrope should be titrated against blood pressure.

If severe hypotension persists despite the above measures, then central venous pressure monitoring should be considered.

Supportive measures are indicated depending on the patient’s clinical state.

Benzodiazepines are not significantly removed from the body by dialysis.

Flumazenil, a benzodiazepine antagonist, is not advised as a routine diagnostic test in patients with reduced conscious level. It may sometimes be used as an alternative to ventilation in children who are naive to benzodiazepines, or in patients with COPD to avoid the need for ventilation. It is not necessary or appropriate in cases of poisoning to fully reverse the benzodiazepine effect. Flumazenil has a short half-life (about an hour) and in this situation an infusion may therefore be required. Flumazenil is contraindicated when patients have ingested multiple medicines, especially after co-ingestion of a benzodiazepine and a tricyclic antidepressant or any other drug that causes seizures. This is because the benzodiazepine may be suppressing seizures induced by the second drug; its antagonism by flumazenil can reveal severe status epilepticus that is very difficult to control.

Contraindications to the use of flumazenil include features suggestive of a tricyclic antidepressant ingestion including a wide QRS, or large pupils. Use in patients' postcardiac arrest is also contraindicated.

It should be used with caution in patients with a history of seizures, head injury, or chronic benzodiazepine use.

Occasionally a respirator may be required but generally few problems are encountered, although behavioural changes are likely in children.

If excitation occurs, barbiturates should not be used.

Effects of overdose are more severe when taken with centrally-acting drugs, especially alcohol, and in the absence of supportive measures, may prove fatal.

24 months.

Store below 25°C. Do not freeze.

2ml glass type 1 ampoules in cartons of 10.

Not applicable.