NEW ZEALAND DATA SHEET 1. PRODUCT NAME NAROPIN 2 mg/mL WITH FENTANYL 2 microgram/mL (ropivacaine hydrochloride plus fentanyl citrate) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each mL of solution for infusion contains ropivacaine hydrochloride 2mg and fentanyl citrate 2microgram. For full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM NAROPIN WITH FENTANYL is a sterile, isotonic solution with nominal osmolality of 288 mOsmol/kg and pH of 4.0 – 6.0. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Acute Pain Management: Continuous epidural infusion e.g. postoperative or labour pain. 4.2 Dose and method of administration Tolerability varies between patients. The lowest dosage that results in effective analgesia should be used and should be based on the status of the patient and the analgesia required. Careful observation of the patient must be maintained during the infusion. Adults Recommended doses for NAROPIN WITH FENTANYL for injection in the average healthy 70 kg adult for up to 72 hours. Epidural administration Continuous infusion Volume Dosage mL/hour Ropivacaine Fentanyl Naropin 2 mg/mL + Fentanyl 2 microgram/mL 6-14 12-28 mg/hr 12-28 microgram/ hr Children Until further experience has been gained, NAROPIN WITH FENTANYL cannot be recommended for use in children below the age of 12 years. Elderly or debilitated patients Debilitated or elderly patients, including those with partial or complete heart conduction block, advanced liver disease or severe renal dysfunction should be given reduced dosage commensurate with their physical condition. Clinical studies with this group of patients have not been performed. (See section 4.4). NAROPIN WITH FENTANYL Data Sheet 2 Test Dose For epidural analgesia, a 3-5 mL test dose of a local anaesthetic, preferably containing up to 5 microgram of adrenaline (e.g. Xylocaine 2% with Adrenaline 1:200,000), should be administered. Verbal contact and repeated monitoring of the heart rate and blood pressure should be maintained for 5 minutes following the test dose after which, in the absence of signs of intravascular or intrathecal injection, the main dose may be administered. An inadvertent intravascular injection may be recognised by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block. If toxic symptoms or signs occur, the infusion should be stopped immediately. Analgesia When calculating the dosage for postoperative analgesia, the use of intraoperative local anaesthetics and opioids should be taken into account. When prolonged blocks are used, either by continuous infusion or repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing local neural injury must be considered. Cumulative doses of up to 800 mg ropivacaine for surgery and postoperative analgesia administered over 24 hours were well tolerated, as were postoperative continuous epidural infusions of ropivacaine with 2 microgram fentanyl at rates up to 14 mL/hour for 72 hours. 4.3 Contraindications 1. Hypersensitivity NAROPIN WITH FENTANYL solutions are contraindicated in patients with known hypersensitivity to local anaesthetics of the amide type or a known intolerance to fentanyl. 2. Bronchial asthma. See also section 4.4. 3. Head injuries and increased intracranial pressure – As for any opioid analgesic, fentanyl should not be used in patients 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. 4. Concomitant MAO Inhibitors Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics and the use of fentanyl in patients who have received MAO inhibitors within 14 days is not recommended. (See section 4.5). 5. Myasthenia gravis Fentanyl may cause muscle rigidity upon IV administration. Therefore, the need for reversal and muscle relaxants contraindicates its use in patients with a history of myasthenia gravis. 4.4 Special warnings and precautions for use Regional anaesthetic procedures should always be performed in a properly equipped and staffed area. Equipment and medicines necessary for monitoring and emergency resuscitation should be immediately available. Patients receiving major blocks should have an IV line inserted before the blocking procedure. The clinician responsible should be appropriately trained and familiar with diagnosis and treatment of side effects, systemic toxicity and other complications. (See section 4.9). NAROPIN AND FENTANYL Data Sheet Copyright 3 Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver disease or severe renal dysfunction require special attention although regional anaesthesia is frequently the optimal anaesthetic technique in these patients. To reduce the risk of potentially serious adverse reactions, attempts should be made to optimise the patient’s condition before major blocks are performed, and the dosage should be adjusted accordingly. Patients treated with anti- arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive. There have been rare reports of cardiac arrest during the use of NAROPIN for epidural anaesthesia of peripheral nerve blockade, especially after unintentional accidental intravascular administration in elderly patients and in patients with concomitant heart disease. In some instances, resuscitation has been difficult. Should cardiac arrest occur, prolonged resuscitative efforts may be required to improve the possibility of a successful outcome. NAROPIN is metabolised in the liver and should therefore be used with caution in patients with severe liver disease and repeated doses may need to be reduced due to delayed elimination. Normally there is no need to modify the dose in patients with impaired renal function when used for single dose or short term treatment. Acidosis and reduced plasma protein concentration, frequently seen in patients with chronic renal failure may increase the risk of systemic toxicity (see section 4.2). Epidural anaesthesia may lead to hypotension and bradycardia. The risk of such effects can be reduced, e.g. by injecting a vasopressor. Hypotension should be treated promptly with a sympathomimetic, repeated as necessary. Adequate facilities should be available for post-operative monitoring and ventilation. Resuscitative equipment, oxygen and a opioid antagonist should be readily available to manage apnoea. NAROPIN is possibly porphyrinogenic and should only be prescribed to patients with acute porphyria when no safer alternative is available. Appropriate precautions should be taken in the case of vulnerable patients. NAROPIN WITH FENTANYL should be used with caution in patients with severe impairment of pulmonary function because of the possibility of respiratory depression (e.g. chronic obstructive pulmonary disease, patients with decreased respiratory reserve, or any patient with potentially compromised respiration). In such patients, opioids may further decrease respiratory drive and increase airway resistance. Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists. Consult individual product information (nalorphine or naloxone) before employing opioid antagonists. Fentanyl may cause muscle rigidity, particularly involving the muscles of respiration. This effect is related to the dose and speed of injection and may be reduced by slow infusion. It is likely to arise following epidural injection. However, if this effect occurs, it may be managed by the use of assisted or controlled respiration and, if necessary, by administration of a neuromuscular blocking agent compatible with the patient’s condition. Nonepileptic myoclonic movements can occur. Fentanyl should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs. Fentanyl may produce bradycardia, which may be treated with atropine; however, it should be used with caution in patients with cardiac bradyarrhythmias. NAROPIN AND FENTANYL Data Sheet Copyright 4 As has been observed with all opioid analgesics, episodes suggestive of Sphincter of Oddi Spasm may occur with fentanyl. Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) Fentanyl is not recommended for use in patients who require the concomitant administration of MAOIs due to the risk of serotonin toxicity (see section 4.5). Concomitant use of Benzodiazepines and other Central Nervous System (CNS) Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of fentanyl with benzodiazepines or other CNS depressants (e.g., non- benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anaesthetics, medicines with antihistamine-sedating actions such as antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of medicine-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid