RAPIFEN INTENSIVE CARE

4). Method of Administration For intravenous infusion. Dosage Adults Rapifen Intensive Care 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 Rapifen Intensive Care). 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. Patients with liver impairment and hypothyroidism will require lower doses. Obese patients may require a dose based on their lean body mass.

The maximum recommended duration of treatment with alfentanil infusions is 4 days. 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.

Elderly and debilitated patients A reduced initial dose is recommended in elderly (>65 years of age) and in debilitated patients. The effect of the initial dose should be taken into account in determining supplemental doses. Paediatric patients Not recommended for use in children in intensive care.

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 Table 1 Adverse Reactions reported in clinical trials and/or postmarketing Frequency Category 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 Rapifen 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.

Warnings:

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)For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses. 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. Drug withdrawal syndrome Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with alfentanil.

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.

The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

Neonatal Withdrawal Syndrome If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome. 6). 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. Cardiovascular warnings Following administration of Rapifen Intensive Care, 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 Rapifen Intensive Care 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.

Muscle rigidity (morphine-like effect) may occur, in which case neuromuscular blocking drugs may be helpful. Risk from concomitant use of Central Nervous System (CNS) depressants, especially benzodiazepines or related drugs Concomitant use of Rapifen and CNS depressants especially benzodiazepines or related drugs in spontaneous breathing patients, may increase the risk of profound sedation, respiratory depression, coma and death.

The concomitant use of opioids and gabapentinoids (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression and death. If a decision is made to administer Rapifen concomitantly with a CNS depressant, especially a benzodiazepine or a related drug, the lowest effective dose of both drugs should be administered, for the shortest period of concomitant use.

Patients should be carefully monitored for signs and symptoms of respiratory depression and profound sedation. In this respect, it is […]

Known intolerance of alfentanil or other morphinomimetics. Pregnancy, and concurrent administration with monoamine oxidase inhibitors.