Alfentanil Other names: Alfentanyl

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 alfentanil and drugs which may depress the heart or increase vagal tone, such as beta-blockers and anaesthetic agents, may predispose to bradycardia or hypotension.

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.

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.

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.

In hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism and liver or renal impairment the dosage of alfentanil 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.

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.

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.

Labour and Delivery

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.

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 medicine is likely to affect your ability to drive.
• Do not drive until you know how the medicine affects you.
• It is an offence to drive while under the influence of this medicine.
• However, you would not be committing an offence (called ‘statutory defence’) if:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
  • It was not affecting your ability to drive safely.

Adverse Reactions

The most frequently reported Adverse reactions (incidence ≥10%) are: nausea and vomiting. Undesirable effects listed below 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’.

Adverse Reactions reported in clinical trials and/or postmarketing:

Immune System Disorders

Not Known: Hypersensitivity (including anaphylactic reaction, anaphylactoid reaction and urticaria

Psychiatric Disorders

Common: Euphoric Mood

Rare: Agitation; Crying

Disorientation

Nervous System Disorders

Common: Movement Disorder; Dizziness; Sedation; Dyskinesia

Uncommon: Headache; Somnolence; Unresponsive to Stimuli

Not Known: Loss of Consciousness (postoperative period); Convulsion; Myoclonus

Eye Disorders

Common: Visual Disturbance

Not Known: Miosis

Cardiac Disorders

Common: Bradycardia; Tachycardia

Uncommon: Arrhythmia; Heart Rate Decreased

Not Known: Cardiac Arrest

Vascular Disorders

Common: Hypotension; Hypertension; Blood Pressure Decreased; Blood Pressure Increased

Rare: Vein Pain

Respiratory, Thoracic and Mediastinal Disorders

Common: Apnoea

Uncommon: Hiccups; Hypercapnia; Laryngospasm; Respiratory Depression (including fatal outcome)

Rare: Bronchospasm; Epistaxis

Not Known: Respiratory Arrest; Cough

Gastrointestinal Disorders

Very Common: Nausea; Vomiting

Skin and Subcutaneous Tissue Disorders

Uncommon: Dermatitis Allergic; Hyperhidrosis

Rare: Pruritus

Not Known: Erythema; Rash

Musculoskeletal and Connective Tissue Disorders

Common: Muscle Rigidity

Renal and urinary disorders

Uncommon: Urinary retention

General Disorders and Administration Site Conditions

Common: Chills; Injection Site Pain; Fatigue

Uncommon: Pain

Not Known: Pyrexia

Injury, Poisoning and Procedural Complications

Common: Procedural Pain

Uncommon: Agitation Postoperative; Airway Complication of Anaesthesia; Confusion Postoperative

Rare: 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.