ALFENTANIL

4). At the proposed doses, Alfentanil 5 mg/ml solution for injection has no sedative activity. Therefore supplementation with an appropriate hypnotic or sedative agent is recommended. Admixture is not advisable due to the need to individually titrate both agents.

Alfentanil given by infusion should only be given in areas where facilities are available to deal with respiratory depression and where continuous monitoring is performed. Alfentanil should only be prescribed by physicians familiar with the use of potent opioids when given by continuous iv infusion.

Dosage Adults Alfentanil 5 mg/ml solution for injection should be diluted with sodium chloride intravenous infusion BP, glucose intravenous infusion BP, or compound sodium lactate intravenous infusion BP (Hartmann’s solution). Such dilutions are compatible with plastic bags and giving sets.

These dilutions should be used within 24 hours of preparation. 4 ml per hour) of undiluted Alfentanil 5 mg/ml solution for injection. For a 70 kg patient, this corresponds to approximately 30 micrograms per kilogram per hour. More rapid control may initially be gained by using a loading dose.

For example, a dose of 5 mg may be given in divided doses over a period of 10 minutes, during which time careful monitoring of blood pressure and heart rate should be performed. If hypotension or bradycardia occurs, the rate of administration should be reduced accordingly and other appropriate measures instituted.

The dose to produce the desired effects should then be individually determined and reassessed regularly to ensure that the optimum dose is being used. 5 to 10 mg alfentanil per hour. 0 mg alfentanil may be given to provide analgesia during short painful procedures.

The maximum recommended duration of treatment with alfentanil infusions is 4 days. Paediatric patients Alfentanil 5 mg/ml solution for injection is not recommended for use in children in intensive care. 2 but no recommendation on a posology can be made.

Elderly and debilitated patients The elderly (>65 years of age) and those patients with liver impairment and hypothyroidism will require lower doses. Obese patients may require a dose based on their lean body mass. Present data suggest that clearance of alfentanil is unaltered in renal failure.

However, there is an increased free fraction and hence dosage requirements may be less than in the patient with normal renal function. Method of administration For intravenous infusion.

Adverse Reactions The most frequently reported Adverse reactions (incidence ≥10%) are: nausea and vomiting. Undesirable effects listed below in Table 1 have been reported in clinical trials (1157 subjects) and/or from spontaneous reports from post-marketing experience.

The following terms and frequencies are applied:

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); and not known (cannot be estimated from the available clinical trial data). Adverse reactions from spontaneous reports during worldwide postmarketing experience with alfentanil that met threshold criteria are included.

Unlike for clinical trials, precise frequencies cannot be provided for spontaneous reports. The frequency for these reports is therefore classified as 'not known'. 4) Nervous System Disorders Movement Disorder; Dizziness; Sedation; Dyskinesia Headache; Somnolence; Unresponsive to Stimuli Loss of Consciousness (postoperative period); Convulsion; Myoclonus Eye Disorders Visual Disturbance Miosis Cardiac Disorders Bradycardia; Tachycardia Arrhythmia; Heart Rate Decreased Cardiac Arrest Vascular Disorders Hypotension; Hypertension; Blood Pressure Decreased; Blood Pressure Increased Vein Pain Respiratory, Thoracic and Mediastinal Disorders Apnoea Hiccups; Hypercapnia; Laryngospasm; Respiratory Depression (including fatal outcome) Bronchospasm; Epistaxis Respiratory Arrest; Cough Gastrointestinal Disorders Nausea; Vomiting Skin and Subcutaneous Tissue Disorders Dermatitis Allergic; Hyperhidrosis Pruritus Erythema; Rash Musculoskeletal and Connective Tissue Disorders Muscle Rigidity Renal and urinary disorders Urinary retention General Disorders and Administration Site Conditions Chills; Injection Site Pain; Fatigue Pain, drug withdrawal syndrome Pyrexia Injury, Poisoning and Procedural Complications Procedural Pain Agitation Postoperative; Airway Complication of Anaesthesia; Confusion Postoperative Anaesthetic Complication Neurological; Procedural Complication; Endotracheal Intubation Complication Paediatric population Frequency, type and severity of adverse reactions in children are expected to be the same as in adults, with the exception of the following: Mild to moderate muscle rigidity has been seen frequently in neonates, although the number of neonates included in clinical studies was small.

Severe rigidity and jerking can occur less commonly and may be accompanied by transient impaired ventilation, especially with high doses of Alfentanil or with a rapid rate of intravenous injection. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Warnings:

Following administration of Alfentanil 5 mg/ml solution for injection, a fall in blood pressure may occur. The magnitude of this effect may be exaggerated in the hypovolaemic patient or in the presence of concomitant sedative medication.

Appropriate measures to maintain a stable arterial pressure should be taken. Like other opioids, alfentanil may cause bradycardia, an effect which may be marked and rapid in onset but which can be antagonised by atropine. Particular care must be taken following treatment with drugs which may depress the heart or increase vagal tone, such as anaesthetic agents or beta-blockers, since they may predispose to bradycardia or hypotension.

Heart rate and blood pressure should therefore be monitored carefully. If hypotension or bradycardia occurs, the rate of administration of alfentanil should be reduced and other appropriate measures instituted. Cardiac arrest following bradycardia has been reported on very rare occasions in non- atropinised patients.

Therefore it is advisable to be prepared to administer an anticholinergic drug. Care must be taken if the patient has received monoamine oxidase inhibitors within the previous 2 weeks. Significant respiratory depression and loss of consciousness will occur following administration of Alfentanil 5 mg/ml solution for injection in doses in excess of 1 mg and is dose-related.

If necessary for assessment purposes, naloxone or other specific antagonists may be administered to reverse the opioid respiratory depression and other pharmacological effects of alfentanil. More than one dose of naloxone may be required in view of its short half life.

Hyperalgesia Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance.

Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Alfentanil 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 Alfentanil 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). Muscle rigidity (morphine-like effect) may occur, in which case neuromuscular blocking drugs may be helpful.

Precautions:

It is wise to reduce the dosage in the elderly and debilitated patient. In hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism and liver or renal impairment the dosage should be titrated with care and prolonged monitoring may be required.

Patients on chronic opioid therapy or with a history of opioid abuse may require higher doses. Non-epileptic (myo)clonic movements can occur. As with all potent opioids, profound analgesia is accompanied by marked respiratory depression, which may persist into or recur in the early post infusion period.

Care should therefore be taken throughout the weaning period and adequate spontaneous respiration should be established and maintained in the absence of stimulation or ventilatory support. Resuscitation equipment and opioid antagonists should be readily available.

Following cessation of the infusion, the patient should be closely observed for at least 6 hours. Prior use of opioid medication may enhance or prolong the respiratory depressant effects of alfentanil. The use of rapid bolus injections of opioids should be avoided in patients with compromised intracerebral compliance; in such patients a transient decrease in the mean arterial pressure has occasionally been accompanied by a transient reduction of the cerebral perfusion pressure.

Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence and opioid use disorder (OUD) may develop upon repeated administration of opioids. 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. 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 […]

1. Obstructive airway disease or respiratory depression if not ventilating. Concurrent administration with monoamine oxidase inhibitors or within 2 weeks of their discontinuation. Administration in labour or before clamping of the cord during Caesarean section due to the possibility of respiratory depression in the new-born infant.