Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: hameln pharma plus gmbh, Langes Feld 13, D-31789, Hameln, Germany
Hypersensitivity to the active substance, to other opioids, or to any of the excipients listed in section 6.1.
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 Caesarian section due to the possibility of respiratory depression in the new-born infant.
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.
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. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).
Muscle rigidity (morphine-like effect) may occur, in which case neuromuscular blocking drugs may be helpful.
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.
This medicine contains less than 1 mmol sodium (23 mg) per each 5mg dose, that is to say essentially 'sodium-free'
The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).
Drugs such as barbiturates, neuroleptics, general anaesthetics and other non-selective CNS depressants (e.g. alcohol) may enhance or prolong the respiratory depressant effects of opioids. If other narcotic or CNS depressant drugs are used concurrently with alfentanil, the effects of the drugs can be expected to be additive. When patients have received such drugs, the dose of alfentanil required will be less than usual. Concomitant use with Alfentanil 5 mg/ml solution for injection in spontaneously breathing patients may increase the risk of respiratory depression, profound sedation, coma, and death.
Following the administration of alfentanil, the dose of other CNS-depressant drugs should be reduced. This is particularly important after surgery, because profound analgesia is accompanied by marked respiratory depression, which can persist or recur in the postoperative period. Administration of a CNS depressant, such as a benzodiazepine, during this period may disproportionally increase the risk for respiratory depression (see above).
In combination with alfentanil, the blood concentrations of propofol are 17% higher than in the absence of alfentanil. The concomitant use of alfentanil and propofol may require a lower dose of Alfentanil 5 mg/ml solution for injection.
Alfentanil is metabolised mainly via the human cytochrome P450 3A4 enzyme. In vitro data suggest that potent cytochrome P450 3A4 enzyme inhibitors (e.g., ketoconazole, itraconazole, ritonavir) may inhibit the metabolism of alfentanil. Available human pharmacokinetic data indicate that the metabolism of alfentanil is inhibited by fluconazole, voriconazole, erythromycin, diltiazem and cimetidine (known cytochrome P450 3A4 enzyme inhibitors). This could increase the risk of prolonged or delayed respiratory depression. The concomitant use of such drugs requires special patient care and observation; in particular, it may be necessary to lower the dose of Alfentanil 5 mg/ml solution for injection.
Treatment with drugs which may depress the heart or increase vagal tone, such as beta-blockers and anaesthetic agents, may predispose to bradycardia or hypotension. Bradycardia and possibly cardiac arrest can occur when Alfentanil 5 mg/ml solution for injection is combined with non-vagolytic muscle relaxants.
It is usually recommended to discontinue MAO-inhibitors 2 weeks prior to any surgical or anaesthetic procedure.
Coadministration of alfentanil with a serotonergic agent, such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), or Monoamine Oxidase Inhibitors (MAOIs), may increase the risk of serotonin syndrome, a potentially life-threatening condition.
Although no teratogenic or acute embryotoxic effects have been observed in animal experiments, insufficient data are available to evaluate any harmful effects in humans.
Consequently, it is necessary to consider possible risks and potential advantages before administering this drug to pregnant patients.
Intravenous administration during childbirth (including caesarian section) is not recommended because Alfentanil crosses the placenta and because the foetal respiratory centre is particularly sensitive to opioids. If Alfentanil is administered nevertheless, assisted ventilation equipment must be immediately available for use if required.
An opioid antagonist for the child must always be available. The half-life of the opioid antagonist may be shorter than the half-life of alfentanil, therefore, repeated administration of the opioid antagonist must be considered.
Alfentanil may appear in breast milk. Therefore, breast-feeding or use of expressed breast milk is not recommended within 24 hours following the administration of Alfentanil.
No studies on the effects of alfentanil on the ability to drive and use machines have been performed.
However, where early discharge is envisaged patients should be advised not to drive or operate machinery for at least 24 hours following administration.
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
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 postmarketing 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’.
Table 1. Adverse Reactions reported in clinical trials and/or postmarketing:
Not Known: Hypersensitivity (including anaphylactic reaction, anaphylactoid reaction and urticaria
Common: Euphoric Mood
Rare: Agitation; Crying
Disorientation
Common: Movement Disorder; Dizziness; Sedation; Dyskinesia
Uncommon: Headache; Somnolence; Unresponsive to Stimuli
Not Known: Loss of Consciousness (postoperative period); Convulsion; Myoclonus
Common: Visual Disturbance
Not Known: Miosis
Common: Bradycardia; Tachycardia
Uncommon: Arrhythmia; Heart Rate Decreased
Not Known: Cardiac Arrest
Common: Hypotension; Hypertension; Blood Pressure Decreased; Blood Pressure Increased
Rare: Vein Pain
Common: Apnoea
Uncommon: Hiccups; Hypercapnia; Laryngospasm; Respiratory Depression (including fatal outcome)
Rare: Bronchospasm; Epistaxis
Not Known: Respiratory Arrest; Cough
Very Common: Nausea; Vomiting
Uncommon: Dermatitis Allergic; Hyperhidrosis
Rare: Pruritus
Not Known: Erythema; Rash
Common: Muscle Rigidity
Uncommon: Urinary retention
Common: Chills; Injection Site Pain; Fatigue
Uncommon: Pain
Not Known: Pyrexia
Common: Procedural Pain
Uncommon: Agitation Postoperative; Airway Complication of Anaesthesia; Confusion Postoperative
Rare: Anaesthetic Complication Neurological; Procedural Complication; Endotracheal Intubation Complication
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 suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme – Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
This medicinal product must not be mixed with other medicinal products except those mentioned in 6.6.
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