THIOPENTAL Powder for solution for injection Ref.[8346] Active ingredients: Thiopental

Posology

Using of thiopental is reserved only for health care personnel trained in anaesthesiology. A person qualified in the use of anesthetics should be constantly available during the administration of the medicinal product.

After continuous administration of thiopental the effect duration is prolonged, personnel qualified in the use of anesthetics should be constantly available during the administration of the medicinal product.

A normal adult dose for induction of anaesthesia is 4-6 mg/kg body weight, but the individual response to the drug is so varied that there can be no fixed dosage. The drug should be titrated against patient requirements as governed by age, sex, body weight and the patient’s general condition. The dose should usually be reduced and carefully titrated in patients with a poor general condition. Younger patients require relatively larger doses than middle-aged and elderly persons; the latter metabolize the drug more slowly. Pre-puberty requirements are the same for both sexes, but adult females require less than adult males. Dose is usually proportional to body weight and obese patients require a larger dose than relatively lean persons of the same weight.

Test Dose

It is advisable to inject a small intravenous “test” dose of 25 to 75 mg (1 to 3 ml of a 2.5% solution) to assess tolerance or unusual sensitivity to thiopental and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities:

1. The patient may be unusually sensitive to thiopental.
2. The solution may be more concentrated than had been assumed.
3. The patient may have received too much premedication.

If the test dose results in local or regional pain, extravasal or intraarterial administration should be suspected (see section 4.4.).

Use in Anesthesia

Moderately slow induction can usually be accomplished in a healthy female or male adult weighing 60-80 kg by injection of 50 to 75 mg of thiopental at intervals of 20 to 40 seconds, depending on the reaction of the patient. Once anesthesia is established, additional injections of 25 to 50 mg can be given whenever the patient moves. Slow injection is recommended to minimize respiratory depression and the possibility of overdosage.

The smallest dose consistent with attaining the surgical objective is the desired goal. Momentary apnea following each injection is typical, and progressive decrease in the amplitude of respiration appears with increasing dosage. Pulse remains normal or increases slightly and returns to normal.

Muscles usually relax about 30 seconds after unconsciousness is attained, but this may be masked if a skeletal muscle relaxant is used.

The tone of jaw muscles is a fairly reliable index. The pupils may dilate but later contract.

Sensitivity to light is not usually lost until a level of anesthesia deep enough to permit surgery is attained. Nystagmus and divergent strabismus are characteristic during early stages, but at the level of surgical anesthesia, the eyes are central and fixed. Corneal and conjunctival reflexes disappear during surgical anesthesia.

When thiopental is used as the sole anesthetic agent, the desired level of anesthesia can be maintained by injection of small repeated doses as needed or by using a continuous intravenous infusion with a 0.2% or 0.4% concentration (see section 6.6). For information on preparation of solutions see section 6.6.

With continuous infusion, the depth of anesthesia is controlled by adjusting the rate of infusion.

Paediatric population

The doses are recommended for healthy paediatric population, and doses may have to be adjusted depending on for example concomitant illness, preanesthesia.

Newborns: IV 3 to 4 mg/kg then 1 mg/kg as needed

Infants: IV 5 to 8 mg/kg then 1 mg/kg as needed.

Children: IV 5 to 6 mg/kg then 1 mg/kg as needed.

The suggested paediatric dosage categories are only indicative of required doses. Actual dosing must be individualized and titrated to effect based on age, maturity and the general condition of the paediatric patient.

Use in convulsive states

75 mg to 125 mg (3mls to 5mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsions following the use of a local anaesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Paediatric population

Intravenously 2 mg/kg initially and then individually titrated until satisfactorily clinical effect has been established. A maximum dose of 5 mg/kg/h should not be exceeded.

Use in neurological patients with raised intracranial pressure

Intermittent bolus injections of 1.5 to 3mg/kg of bodyweight may be given to reduce elevations of intracranial pressure if controlled ventilation is provided.

Paediatric population

The safety of thiopental in paediatric populations to treat raised intracranial pressure has not yet been established.

Hepatic impairment

Reduced dose should be used in patients with hepatic impairment (see section 4.4).

Renal impairment

Thiopental should be used with caution in patients with renal impairment (see section 4.4).

Method of administration

This medicinal product must only be administered by the intravenous route. Care should be taken to ensure intravenous administration (see section 4.4). For instructions on dilution of the medicinal product before administration, see section 6.6. Infusion should only be given through a central venous catheter.

Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by an alarming fall in blood pressure and shock. Apnea may occur in connection with too excessive or too rapid injections. Also laryngospasm, coughing and other respiratory difficulties may occur, but may also be a sign of under dosing (reflex induced).

In the event of suspected or apparent overdosage, the drug should be discontinued. A patent airway should be secured. Oxygenation and ventilation should be monitored and supported as needed. The circulation should be monitored and supported as needed.

Shelf life: 3 years.

Shelf-life after reconstitution:

Chemical and physical in-use stability has been demonstrated for 9 hours below 25°C and 24 hours at 2°C to 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C.

This medicinal product does not require any special storage conditions.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

For single use after reconstitution. Discard any remainder after use.

20 mL vials made from colourless type III glass with a rubber stopper, aluminium seal and a polypropylene flip-off cap.

Pack size: 1, 10, 25 and 50 vials.

Not all pack sizes may be marketed.

Solutions should be prepared aseptically with one of the three following diluents:

• Sterile Water for Injection (according Ph.Eur.),
• solution for infusion of sodium chloride (9 mg/ml),
• 5% dextrose solution for infusion.

Clinical concentrations used for intermittent intravenous administration vary between 2.0% and 5.0%.

A 2.0% or 2.5% solution is most commonly used. A 3.4% concentration in sterile water for injection is isotonic; concentrations less than 2.0% in this diluent are not used because they cause hemolysis. For continuous intravenous drip administration, concentrations of 0.2% or 0.4% are used. Solutions may be prepared by adding thiopental to 5% water solution of dextrose or to 0.9% solution of sodium chloride.

Calculations for various concentrations:

Since this medicinal product contains no added bacteriostatic agent, extreme care in preparation and handling should be exercised at all times to prevent the introduction of microbial contaminants.

Solutions should be freshly prepared and used promptly; when reconstituted for administration to several patients; unused portions should be discarded after 24 hours. Sterilization by vapour should not be attempted.

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