BUPIVADREN

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

Bupivadren contains two active ingredients: adrenalin (epinephrine) and bupivacaine hydrochloride.

Bupivacaine is combined with adrenaline (epinephrine) to make it last longer. Bupivadren belongs to a group of medicines called local anaesthetics.

Bupivadren is used to prevent or relieve pain, including in childbirth and after surgery, but it will not put you to sleep.

For more information, see Section 1. Why am I using Bupivadren? in the full CMI.

Do not use if you have ever had an allergic reaction to adrenaline (epinephrine) acid tartrate, bupivacaine hydrochloride monohydrate, other local anaesthetics e.g. lignocaine, or any of the ingredients listed at the end of the CMI.
Do not use if you have severe heart disease, thyrotoxicosis (hyperthyroidism) or blood poisoning.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use Bupivadren? in the full CMI.

Some medicines may interfere with Bupivadren and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

• Bupivadren is given in a clinical setting by a doctor or nurse.
• Bupivadren will be injected by your doctor into the skin, near a single nerve, or into an area which contains a large number of nerves.

More instructions can be found in Section 4. How is Bupivadren used? in the full CMI.

For more information, see Section 5. What should I know while using Bupivadren? in the full CMI.

Less serious side effects: nausea or vomiting; lightheaded or dizziness; blurred or double vision; ringing in the ears; a tingling feeling or numbness; sensations of hot or cold; feeling strange, anxious, nervous, restless or euphoric; confusion or agitation; inability to tolerate sound; racing heart; headache; inability to pass urine; muscle weakness, twitching or tremors; numbness of the tongue, difficulty swallowing or slurred speech.
More serious side effects: loss of bladder or bowel control, sexual function, movement of the lower body; unusual burning or stinging pain; fits; breathing problems; low blood pressure; slow heartbeat; unconsciousness or collapse.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

Boxed Warnings

Not for intravenous administration under any circumstances.

1 Name of Medicine

Bupivacaine hydrochloride (as monohydrate).
Adrenaline (epinephrine) acid tartrate.

2 Qualitative and Quantitative Composition

Bupivadren bupivacaine 0.25% w/v with adrenaline (epinephrine) 1:400,000 injection vial contains bupivacaine hydrochloride 2.5 mg/mL with adrenaline (epinephrine) 2.5 microgram/mL.
Bupivadren bupivacaine 0.5% w/v with adrenaline (epinephrine) 1:200,000 injection vial contains bupivacaine hydrochloride 5 mg/mL with adrenaline (epinephrine) 5 microgram/mL.
Excipient(s) with known effect. Sodium metabisulfite.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Bupivadren is a sterile solution for injection. The solutions are practically free from visible particles.
Bupivadren solution for injection is a sterile, isotonic aqueous solution of bupivacaine hydrochloride monohydrate, adrenaline (epinephrine) acid tartrate and sodium chloride in Water for Injections BP. The pH of the solution is adjusted with citric acid and sodium citrate dihydrate to remain between 3.3 - 5.0. Bupivadren contain sodium metabisulfite as an antioxidant.

4 Clinical Particulars

4.9 Overdose

Acute emergencies associated with the use of local anaesthetics are generally related to high plasma levels or to unintended subarachnoid injection of the local anaesthetic solution (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.4 Special Warnings and Precautions for Use).
With accidental intravascular injections of local anaesthetics, the toxic effects will be obvious within 1-3 minutes. With overdosage, peak plasma concentrations may not be reached for 20-30 minutes, depending on the site of injection and toxic signs will be delayed. Toxic reactions mainly involve the central nervous and cardiovascular systems.
Symptoms of acute toxicity. Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are circumoral paraesthesia, numbness of the tongue, lightheadedness, hyperacusis and tinnitus. Visual disturbances and muscular tremors are more serious and precede the onset of generalised convulsions. These signs must not be mistaken for neurotic behaviour.
Unconsciousness and grand mal convulsions may follow. These may last from a few seconds to several minutes. Hypoxia and hypercapnia occur rapidly following convulsions due to increased muscular activity, together with the interference with normal respiration and loss of the airway. In severe cases, apnoea may occur.
Acidosis, hyperkalaemia, hypocalcaemia and hypoxia increase and extend the toxic effects of local anaesthetics.
Recovery is due to redistribution of the local anaesthetic drug from the central nervous system and metabolism. Recovery may be rapid unless large amounts of the drug have been injected.
Signs of cardiovascular toxicity indicates a more severe situation. Hypotension, bradycardia, decreased cardiac output, heart block, arrhythmia and even ventricular arrhythmias, ventricular fibrillation and cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics.
Overdosage with adrenaline (epinephrine) produces a rapid rise in blood pressure which may result in cerebrovascular haemorrhage, cardiac arrhythmia leading to ventricular fibrillation and death. Pulmonary oedema may also lead to death because of the peripheral constriction and cardiac stimulation produced.
Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as benzodiazepines or barbiturates.
Treatment of overdose. If signs of acute systemic toxicity appear, injection of the local anaesthetic should be immediately stopped.
If convulsions occur then immediate attention is required for the maintenance of patent airway and assisted or controlled ventilation with oxygen, via a positive airway pressure delivery system mask. Adequacy of the circulation should then be evaluated, bearing in mind that drugs used to treat convulsions depress the circulation when administered intravenously.
Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, appropriate anticonvulsant medication such as an ultra-short acting barbiturate (e.g. thiopentone) or a benzodiazepine (e.g. diazepam) may be administered IV. The clinician should be familiar with these anticonvulsant drugs prior to use of local anaesthetics.
Suxamethonium will stop the muscle convulsions rapidly but will require tracheal intubation and controlled ventilation, and should only be used by those familiar with these procedures.
If cardiovascular depression occurs (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressor, inotropic agents and/or lipid emulsion should be considered. Children should be given doses commensurate with age and weight.
If ventricular fibrillation or cardiac arrest occurs, effective cardiovascular resuscitation treatment must be instituted and maintained for a prolonged period if necessary. Optimal oxygenation and ventilation, and circulatory support as well as treatment of acidosis are of vital importance.
To counteract the pressor effects of adrenaline (epinephrine), use rapidly acting vasodilators, for instance nitrates or α-blocking agents.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Formal studies of mutagenic potential have not been carried out.
Carcinogenicity. Long-term studies in animals of most local anaesthetics, including bupivacaine, to evaluate the carcinogenic potential have not been conducted.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

The chemical name for bupivacaine hydrochloride (as monohydrate) is (2RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide hydrochloride monohydrate.
Bupivacaine hydrochloride (as monohydrate) has the chemical formula C₁₈H₂₉ClN₂O,H₂O and molecular weight value 342.9.
The chemical name for adrenaline (epinephrine) acid tartrate is (1R)-1-(3,4-Dihydroxyphenyl)-2-(methylamino)ethanol hydrogen (2R,3R)-2,3-dihydroxybutanedioate.
Adrenaline (epinephrine) acid tartrate has the chemical formula C₁₃H₁₉NO₉ and a molecular weight of 333.3.
Bupivacaine hydrochloride is a white or almost white, crystalline powder or colourless crystal that is soluble in water and freely soluble in ethanol (96%). Bupivacaine has a pKa of 8.1 and is more lipid soluble than lignocaine.
Adrenaline (epinephrine) acid tartrate appears as a white or greyish-white, crystalline powder that is freely soluble in water and slightly soluble in ethanol (96%).
Chemical structure. The chemical structure of bupivacaine hydrochloride (as monohydrate) is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSBUPIHY.gif The chemical structure of adrenaline (epinephrine) acid tartrate is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSDRENAT.gif CAS number. The CAS number for bupivacaine hydrochloride, (as monohydrate) is 73360-54-0.
The CAS number for bupivacaine HCl anhydrous is 18010-40-7.
The CAS number for adrenaline (epinephrine) is 51-43-4.
The CAS number for adrenaline acid tartrate is 51-42-3.

7 Medicine Schedule (Poisons Standard)

Schedule 4 Prescription only medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/BUPIVAST.gif