BUPIVACAINE HYDROCHLORIDE

4). Adults The length of continuous epidural infusions given post-operatively should be minimized, due to the increased risks of reaching a toxic plasma concentration, inducing local neural injury or local infection. Administration of bupivacaine with fentanyl epidural infusion has not been adequately studied for more than 72 hours.

The dosages in the following table are recommended as a guide for use in healthy adults during labour and in the post operative period. It should not be necessary to exceed an infusion dosage of 20 mg/hour for bupivacaine. Standard textbooks should be consulted for factors affecting specific block techniques; dosing should be titrated to meet the individual patient requirements and the lowest dose required to provide adequate analgesia should be used.

75 12 - 30 Careful aspiration before starting the infusion is recommended to prevent intravascular injection. The infusion rate should be slow, with continual assessment of the patient in order to optimise efficacy and safety considerations for the patient and to avoid overdosage.

• Following the start of an infusion a continuous review of the patient is required, including periodic monitoring of the patient’s blood pressure/pulse and assessment of pain and sedation at a minimum of 30 minute intervals. Where conscious, verbal contact with the patient should be maintained throughout.

• Segmental testing of the level of the block is required at least at hourly intervals throughout the time the infusion is administered. Appropriate monitoring should be carried out to detect progressive spread of the block or an increasing density of block.

• Motor block should be assessed periodically using the Bromage score. For obstetric analgesia the test level T5/T6 should be clearly marked, for postoperative analgesia the level of block should be determined relative to the site of surgery.

• Routine maternal cardiovascular and foetal monitoring should be performed. In the case of labour, foetal heart rate should be monitored every 5 minutes for 30 minutes and then as appropriate. Hepatic / Renal Impairment Since bupivacaine and fentanyl are metabolized in the liver and excreted via the kidneys, the possibility of medicine accumulation should be considered in patients with hepatic and/or renal impairment, with a possible reduction in dosage depending on the severity of their impairment.

Adequate filtering should be an integral part of the infusion line. The infusion line should be clearly marked to avoid confusion with intravenous lines. Also to avoid confusion, consideration should be given to using a different brand of proprietary pump to that used for IV infusions.

In addition, the following pump specifications should be considered: • accurate infusion rates down to 1 ml/hour should be able to be set. • positive pressure drive, (not gravity feed), should be present. • a back-up battery should be present.

• an automatic infusion shut-off should be present in case power is lost or the front of the pump is accidentally opened. Elderly Debilitated or elderly patients, including those with advanced liver disease or severe renal dysfunction should be given a reduced dosage commensurate with their physical condition.

Paediatric population The use of bupivacaine with fentanyl in children is not recommended since experience in paediatric patients is limited.

Method of administration:

Epidural use Bupivacaine and Fentanyl solution for infusion should only be administered epidurally and should only be used by or under the supervision of clinicians experienced in regional anaesthesia. The dose administered must be tailored to the individual patient and procedure.

When calculating the dosage for post-operative analgesia, the use of intra-operative bupivacaine and/or fentanyl (or other opioid agonist analgesic) should be taken into account. The rapid injection of bupivacaine with fentanyl solution should be avoided and the maximum accumulated dosage should not exceed 400 mg of bupivacaine and 720 micrograms of fentanyl for a 24 hour period in a 70 kg adult.

Note:

This formulation is not to be used as a bolus.

Bupivacaine Reactions to bupivacaine are similar in character to those observed with other local anaesthetics of the amide type. Adverse reactions may be due to high plasma levels as a result of excessive dosage, rapid absorption, delayed elimination or metabolism, or inadvertent intravascular injection.

Such reactions are systemic in nature and involve the central nervous system and/or the cardiovascular system. Inadvertent subarachnoid injection may lead to cardiovascular collapse, unconsciousness and respiratory arrest. An accidental intrathecal injection may be recognized by early signs of spinal block such as hypotension, bradycardia and difficulty in breathing.

The adverse reactions considered at least possibly related to treatment with bupivacaine hydrochloride from clinical trials with related products and post- marketing experience are listed below by body system organ class and absolute frequency.

Frequencies are defined as 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) including isolated reports, or Not known (identified through post- marketing safety surveillance and the frequency cannot be estimated from the available data).

5) Respiratory, thoracic and mediastinal disorders Rare Laryngospasm, respiratory depression or respiratory arrest Gastrointestinal disorders Very Common Nausea Common Vomiting Renal and urinary disorders Common Urinary retention Fentanyl The following table displays ADRs that have been reported with the use of fentanyl IV from either clinical trials or post-marketing experiences.

) Injury, poisoning and procedural complications Postoperative confusion Airway complicatio ofanaesthesia 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 balanceof the medicinal product. uk/or search for MHRA Yellow Card in the Google Play or Apple App Store.

When any local anaesthetic agent is used, resuscitative equipment and medicines, including oxygen, should be immediately available to manage possible reactions involving the cardiovascular, respiratory or central nervous systems. Spinal and epidural anaesthesia may result in sympathetic block with resultant hypotension and bradycardia, therefore an intravenous cannula should be inserted before the local anaesthetic is injected.

In view of the risk of inadvertent intravascular injection which can produce toxic effects, bupivacaine should be given with great caution to patients with epilepsy, severe bradycardia, cardiac conduction disturbances, severe shock or severe digitalis intoxication.

Patients with uncorrected hypotension, coagulation disorders or patients receiving anti- coagulant treatment should receive epidural local anaesthetics with caution. Bupivacaine hydrochloride should be administered with caution to patients with cardiovascular disease, hypertension, hyperthyroidism or adrenocortical insufficiency.

Fentanyl should be used with caution in patients with cardiac bradyarrhythmias. For continuous epidural analgesia the lowest possible effective concentration of local anaesthetic should be used. This will aid detection of neurological effects that might otherwise be masked by epidural blockade.

Debilitated, elderly or young patients, including those with advanced liver disease orsevere renal impairment, may require reduced doses commensurate with their age and physical condition. Since bupivacaine and fentanyl are metabolized in the liver and excreted via the kidneys, the possibility of medicine accumulation should be considered in patients with hepatic and/or renal impairment.

As has been observed with all narcotic analgesics, episodes suggestive of Sphincter of Oddi Spasm may occur with fentanyl. g. myasthenia gravis. g. meningitis, spinal fluid/ block, cranial or spinal haemorrhage, tumours, poliomyelitis, syphilis, tuberculosis,or metastatic lesions of the spinal cord.

g. bronchial asthma, patients with decreased respiratory reserve, or any patient with potentially compromised respiration) because of the possibility of respiratory depression. In such patients, narcotics may further decrease respiratory drive and increase airway resistance.

Certain forms of conduction anaesthesia, such as spinal anaesthesia and some peridural anaesthetics can alter respiration by blocking intercostal nerves. Fentanyl can also alter respiration through other mechanisms. Therefore, when bupivacaine with fentanyl is used to supplement these forms of anaesthesia, the physician should be familiar with the physiological alterations involved and be prepared to manage them in patients selected for this form of analgesia.

) have not shown cross sensitivity to agents of the amide type. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs: Concomitant use of Bupivacaine and Fentanyl solution for infusion and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Bupivacaine and Fentanyl solution for infusion concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Tolerance and Opioid use disorder (abuse and dependence) Tolerance, physical dependence, and psychological dependence may develop upon repeated administration of opioids.

Repeated use of opioids may lead to Opioid use disorder (OUD). Abuse or intentional misuse of opioids may result in overdose and/or death. g. major depression, anxiety and personality disorders). Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.

A comprehensive patient history should be taken to document concomitant medications, including over the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions. Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced.

Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient. Overuse or misuse may result in overdose and/or death.

It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else. Patients should be closely monitored for signs of misuse, abuse, or addiction.

The clinical need for analgesic treatment should be reviewed regularly. Withdrawal syndrome Prior to starting […]

1 The use of Bupivacaine and Fentanyl solution for infusion is contraindicated in case of: • acute respiratory depression, • acute alcoholism, • raised intracranial pressure or head injury. As for any narcotic analgesic, fentanyl should not be used in patients with or susceptible to respiratory depression, such as comatose patients who may have head injuries or a brain tumour.

Fentanyl may obscure the clinical course of patients with head injury, • hypovolaemia and complete heart block, • intravenous regional anaesthesia (Bier's block) as unintentional passage of local anaesthetic into the systemic circulation, despite the use of a tourniquet, may cause systemic toxic reactions, • obstetrical paracervical block anaesthesia, • concurrent administration of monoamine oxidase inhibitors (MAOI’s) or within 2 weeks of their discontinuation.

Epidural anaesthesia, regardless of the local anaesthetic used, has its own contraindications which include: • active disease of the central nervous system such as meningitis, poliomyelitis, intracranial haemorrhage, subacute combined degeneration of the cord due to pernicious anaemia, spina bifida or meningomyelocele and cerebral or spinal tumours, • tuberculosis of the spine, • inflammation and/or pyogenic infection of the skin at or adjacent to the site of lumbar puncture, • a diagnosed arteriovenous malformation in the vertebral column in close proximity to the proposed puncture site, • cardiogenic shock, • coagulation disorders or ongoing anticoagulant therapy, • an expanding cerebral lesion, a tumour, cyst or abscess, which may, if the intracranial pressure is suddenly altered, cause obstruction to the cerebrospinal fluid or blood circulation (the pressure cone).