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

Thiopental may cause addiction.

Keep endotracheal intubation equipment, oxygen and resuscitative equipment readily available.

Caution must be taken in patients with increased intracranial pressure or asthma.

If used under these conditions reduce dosage and administer slowly.

Use in neurological patients with raised intracranial pressure

Thiopental has been associated with reports of severe or refractory hypokalaemia during infusion; severe rebound hyperkalaemia may occur after cessation of thiopental infusion. The potential for rebound hyperkalaemia should be taken into account when stopping thiopental therapy.

Caution must be taken in patients with potential airway compromise, such as conditions involving inflammation in the mouth, jaw and throat.

Cardiorespiratory depression

Thiopental sodium causes respiratory depression and a reduction in cardiac output and may precipitate acute circulatory failure in patients with cardiovascular disease, particularly constrictive pericarditis. Care should also be exercised with severe cardiovascular diseases, severe respiratory diseases and hypertension of various aetiology.

When particular caution is required

Special care is needed in administering thiopental sodium to patients with the following conditions:- hypovolaemia, severe haemorrhage, burns, cardiovascular disease, myasthenia gravis, adrenocortical insufficiency (even when controlled by cortisone), cachexia, raised intracranial pressure and raised blood urea.

Dose reduction required

Reduced doses are recommended in shock, dehydration, severe anaemia, hyperkalaemia, toxaemia, metabolic disorders e.g. thyrotoxicosis, myxoedema and diabetes.

Increased doses

Increased doses may be necessary in patients who have either a habituation or addiction to alcohol or drugs of abuse. Under these circumstances it is recommended that supplementary analgesic agents are used.

Hepatic impairment

Thiopental sodium is metabolized primarily by the liver so doses should be reduced in patients with hepatic impairment.

Renal impairment

Barbiturate anaesthetics should be used with caution in severe renal disease. Reduced doses are also indicated in the elderly and in patients who have been premedicated with narcotic analgesics.

Use in underlying disease

Patients taking long-term medications such as aspirin, oral anticoagulants, oestrogens, MAOIs and lithium may need to adjust the dose or stop therapy prior to elective surgery. Patients with diabetes or hypertension may need to adjust their therapy before anaesthesia (see section 4.5).

Thiopental concentrations less than 2.0% can cause hemolysis.

Extravascular infiltration

Extravascular injection should be avoided. Care should be taken to insure that the needle is within the lumen of the vein before intravenous injection of this medicinal product. Extravascular injection may cause chemical irritation of the tissues varying from slight tenderness to venospasm, extensive necrosis, severe pain and sloughing. This is due primarily to the high alkaline pH (10 to 11) of clinical concentrations of the drug. If extravasation occurs, the local irritant effects can be reduced by injection of 1% lidocaine locally to relieve pain and enhance vasodilatation. Local application of heat also may help to increase local circulation and removal of the infiltrate (see section 4.8).

Intra-arterial injection

Intra-arterial injection can occur inadvertently, especially if an aberrant superficial artery is present at the medial aspect of the antecubital fossa. The area selected for intravenous injection of the drug should be palpated for detection of an underlying pulsating vessel. Accidental intra-arterial injection may cause arteriospasm and severe pain along the course of the artery with blanching of the arm and fingers. Appropriate corrective measures should be instituted promptly to avoid possible development of gangrene. Methods suggested for dealing with this complication vary with the severity of symptoms (see section 4.8).

The following have been suggested (controlling investigations are missing):

1. Dilute the medicinal product by removing the tourniquet and any restrictive garments.
2. Leave the intravenous cannula in place, if possible.
3. Inject the artery with a dilute solution of papaverine, or lidocaine, to inhibit smooth muscle spasm.
4. If necessary, perform sympathetic block of the brachial plexus and/or stellate ganglion to relieve pain and assist in opening collateral circulation. Papaverine can be injected into the subclavian artery, if desired.
5. Unless otherwise contraindicated, treat with heparin to prevent thrombus formation.
6. Consider local infiltration of an alpha-adrenergic blocking agent such as phentolamine into the vasospastic area.
7. Provide additional symptomatic treatment as required.

This medicinal product contains 106 mg sodium per vial for 1g and 53mg per vial for 500mg. To be taken into consideration by patients on a controlled sodium diet.

Pharmacodynamic interactions

Thiopental sodium has been shown to interact with sulphafurazole. Reduced initial doses may be required to achieve adequate anaesthesia, but repeat doses may also be necessary to maintain anaesthesia.

Gastrointestinal drugs: Metoclopramide and droperidol reduce the dose of thiopental sodium required to induce anaesthesia.

The use of anaesthetics with other CNS depressant drugs such as those used for premedication may produce synergistic effects on the CNS and, in some cases, a smaller dose of general anaesthetic should be used. Bradycardia occurring during anaesthetic induction with thiopental has been reported in patients also receiving fentanyl.

Benzodiazepines: Midazolam potentiates the anaesthetic effects of thiopental sodium.

Probenecid: Pretreatment with probenecid has been shown to potentiate thiopental sodium anaesthesia.

Angiotensin-II receptor antagonists: Enhanced hypotensive effect when general anaesthetics given with angiotensin-II receptor antagonists.

Antibacterials: General anaesthetics possibly potentiate hepatotoxicity of isoniazid; effects of thiopental sodium enhanced by sulphonamides; hypersensitivity-like reactions can occur when general anaesthetics given with intravenous vancomycin.

Antidepressants: Increased risk of arrhythmias and hypotension when general anaesthetics given with tricyclic antidepressants. Hypotension and hypertension has been seen with MAOIs.

Antipsychotics: Patients being treated with phenothiazine antipsychotics may experience increased hypotension. Some phenothiazines, especially promethazine, may also increase the incidence of excitatory phenomena produced by barbiturate anaesthetics; cyclizine may possibly have a similar effect. The sedative properties may be also potentiated by thiopental sodium.

Diazoxide: Enhanced hypotensive effect when general anaesthetics given with diazoxide.

Diuretics: Enhanced hypotensive effect when general anaesthetics given with diuretics.

Methyldopa: enhanced hypotensive effect when general anaesthetics given with methyldopa.

Moxonidine: Enhanced hypotensive effect when general anaesthetics given with moxonidine

Nitrates: Enhanced hypotensive effect when general anaesthetics given with nitrates.

Vasodilator antihypertensives: Enhanced hypotensive effect when general anaesthetics given with hydralazine, minoxidil or nitroprusside.

It should be noted that thiopental will interact with beta-blockers and calcium antagonists causing a fall in blood pressure.

ACE inhibitors: enhanced hypotensive effect when general anaesthetics given with ACE inhibitors.

Adrenergic neuron blockers: Enhanced hypotensive effect when general anaesthetics given with adrenergic neurone blockers.

Alpha-blockers: Enhanced hypotensive effect when general anaesthetics given with alpha-blockers.

Herbal medicines: Animal data suggest valerian and St John’s Wort may prolong the effect of thiopental sodium.

Analgesics: Pretreatment with aspirin has been shown to potentiate thiopental sodium anaesthesia. Opioid analgesics can potentiate the respiratory depressant effect of barbiturate anaesthetics and the dose of anaesthetic may need to be reduced. The analgesic effect of pethidine can be reduced by thiopental sodium.

Opioids potentiate the respiratory depressive effect. The effect is enhanced by alcohol, hypnotics, central acting muscle relaxants, anxiolytics, antipsycotics and antihistamines.

Thiopental interacts with opioid analgesics (decreased sensibility to pain) and sufentanile (decrease dose dependently the need of barbiturates at induction of anaesthesia. Increased doses may be necessary in patients with alcohol- or narcotics misuse.

Pharmacokinetic interactions

Concomitant use of barbiturates and quetiapine may result in a reduced serum concentration of quetiapine.

Barbiturates increase by enzyme induction the elimination of androgens, some antiepileptics, felodipin, glucocorticoids, metronidazole, peroral anticoagulants and estrogen and thereby decrease the plasma concentration of these substances.

Barbiturates inhibit the hypoglycaemic effect of peroral antidiabetics (sulfonyl-urine substances).

Barbiturates inhibit the effect of bronchodilators (aminophylline).

Pregnancy

It has been shown that thiopental can be used without adverse effects during pregnancy. However, when considering use of thiopental the clinician should only use the drug when the expected benefits outweigh any potential risks.

Breast-feeding

Thiopental readily crosses the placental barrier and also appears in breast milk. Animal reproduction studies have not been conducted with thiopental. Therefore, breast-feeding should be temporarily suspended (for at least 12 hours) or breast milk expressed before the induction of anaesthesia.

Fertility

There are no data on the effect of thiopental on human fertility.

This medicinal product has major influence on the ability to drive and use machines. Even though the recovery after use of this medicinal product is rapid; post-operative vertigo, disorientation and sedation may be prolonged and out-patients given thiopental should therefore be advised not to drive or use machinery especially within the first 24 to 36 hours.

The frequencies of adverse events are ranked according to the following:

Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Cardiac disorders

Common: Heart arrhythmia, Myocardia depression, Hypotension

Nervous system disorders

Common: Somnolence, Delayed wakening

Not known: Headache, Confusion, Dizziness, Amnesia

Respiratory, thoracic and mediastinal disorder

Common: Respiratory depression, Bronchospasm, Laryngospasm, Coughing, Snoring, Sneezing

General disorders and administration site conditions

Common: Shivering, Thrombosis, Phlebitis, Pain at the administration site may occur

Not known: Malaise, Fatigue

Metabolism and nutrition disorders

Not known: Hypokalaemia, Hyperkalaemia, Anorexia

Immune system disorders

Rare: Anaphylactoid reactions (urticaria, bronchospasm, fall in blood pressure and angioedema)

Not known: Allergic reactions, Skin reactions, Hypersensitivity, Anaphylactic shock

Gastrointestinal disorders

Not known: Nausea and vomiting

Musculoskeletal and connective tissue disorders

Not known: Involuntary movements and muscle tremor

Renal and urinary disorders

Not known: Renal failure, polyuria (when high doses are used)

Psychiatric disorders

Not known: Unpleasant dream, euphoric or dysphoric mood

Immune hemolytic anemia with renal failure and paralysis of nervus radialis have been reported in rare cases. Reactions which may be caused by the diluent, preparation – or solving technique or by administration of prepared solutions with thiopental sodium include fever, venous thrombosis or phlebitis at the injection site, and events after extravasal injection.

Laryngeal spasm may occur, together with coughing or sneezing, during the induction procedure. For this reason it is not advised to use thiopental sodium alone for peroral endoscopy.

Excessive doses are associated with hypothermia and profound cerebral impairment.

Postoperative vomiting is infrequent, but shivering may occur and there may be persistent drowsiness, confusion and amnesia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

This medicine must not be mixed with other medicinal products except those mentioned in section 6.6.

The solutions prepared with THIOPENTAL are strongly alkaline and are not compatible with volume replacement solutions and acidic anaesthetic adjuvant solutions, since precipitation and clogging of the injection needle may occur. Similarly, chemical changes in the added solution cannot be ruled out.