RIVOTRIL Concentrate for solution for injection / infusion Ref.[28153] Active ingredients: Clonazepam

Rivotril sterile concentrate is for intravenous administration. For the treatment of status epilepticus, the dose and rate of administration are governed by the response of the patient.

Adults

1mg (one ampoule of active substance mixed with one ampoule of solvent for parenteral use) by slow intravenous injection.

Elderly

Care should be taken with the elderly.

Children

0.5mg (equivalent to half an ampoule of active substance mixed with half an ampoule of solvent for parenteral use) by slow intravenous injection.

Special dosage instructions

Rivotril can be administered with one or several other antiepileptic agents, in which case the dosage of each drug must be adjusted to achieve optimum effect.

As with all antiepileptic agents, treatment with Rivotril must not be stopped abruptly, but must be reduced in a stepwise fashion (see section 4.8).

Mode of administration

Rivotril must be diluted prior to administration in order to avoid irritation of the veins, see section 6.6.

Intravenous injection of Rivotril should be into a large vein of the antecubital fossa. The injection should be given slowly – in adults, the rate of injection must not exceed 0.25mg–0.5mg (0.5–1.0ml of the prepared solution) per minute – and should be administered with continuous monitoring of EEG, respiration and blood pressure. This will greatly diminish the rare possibility of hypotension or apnoea occurring. Nevertheless, facilities for resuscitation should always be available. A total dose of 20mg should not be exceeded.

Rivotril sterile concentrate may be diluted when given in intravenous infusions of saline or glucose, such as are customary in the treatment of status epilepticus, see section 6.6

Symptoms

The symptoms of overdosage or intoxication vary greatly from person to person depending on age, bodyweight and individual response. Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of Rivotril is seldom life-threatening if the drug is taken alone, but may lead to coma, areflexia, apnoea, hypotension and cardiorespiratory depression. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease.

Benzodiazepines potentiate the effects of other central nervous system depressants, including alcohol.

Management

1. Maintain a clear airway and adequate ventilation if indicated.
2. Supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.
3. Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients.
4. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure.
5. Patients who are asymptomatic at 4 hours are unlikely to develop symptoms.
6. Flumazenil, a benzodiazepine antagonist is available but should rarely be required. If CNS depression is severe consider the use of flumazenil. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug. Flumazenil is NOT TO BE USED IN MIXED OVERDOSE OR AS A “DIAGNOSTIC TEST”.

Warning

The use of flumazenil is not indicated in patients with epilepsy who have been treated with benzodiazepines. Although flumazenil exerts a slight intrinsic anticonvulsant effect, its abrupt suppression of the protective effect of a benzodiazepine agonist can give rise to convulsions in epileptic patients.

If excitation occurs, barbiturates should not be used.

Unopened ampoules: 4 years.

Shelf-life of diluted product: from a chemical and physical stability point of view, the diluted product is stable up to 12 hours. However, it should be used immediately after dilution in order to reduce the possibility of microbial contamination unless it is diluted under validated aseptic conditions. See section 6.6 for instructions on dilution.

Do not store above 30ºC. Keep the ampoules in the outer carton in order to protect from light.

5 or 10 × 2 ml amber glass ampoules each containing 1 ml active concentrate containing 1mg clonazepam.

5 or 10 × 1 ml clear glass ampoules each containing 1 ml of solvent for parenteral use.

Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.

Preparation of intravenous injection:

The contents of the solvent ampoule, which contains 1ml Water for Injection, must be added to the contents of the other ampoule, which contains 1mg clonazepam in 1ml, immediately before injection.

Preparation of intravenous infusion:

3mg clonazepam (3 ampoules) can be diluted in 250ml of the following solutions:

Sodium Chloride Intravenous Infusion 0.9% w/v

Glucose Intravenous Infusion 5% and 10% Sodium Chloride and Glucose Intravenous Infusion (0.45% sodium chloride and 2.5% glucose)

The active ingredient clonazepam can be absorbed on PVC. It is therefore recommended either glass containers be used or, if PVC infusion bags are used, that the mixture be infused straight away over a period of no longer than 2 hours.

Each ampoule is for single use only. Discard any unused solution after use.