Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adult Dosage

Route of administration

Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway (see section 4.4).

Intravenous administration either as a bolus or by infusion.

Intramuscular administration.

Sublimaze, by the intravenous route, can be administered to both adults and children. The dose of Sublimaze should be individualised according to age, body weight, physical status, underlying pathological condition, use of other drugs and type of surgery and anaesthesia.

Adults

The usual dosage regimen in adults is as follows:

Doses in excess of 200 mcg are for use in anaesthesia only. As a premedicant, 1-2 ml Sublimaze may be given intramuscularly 45 minutes before induction of anaesthesia.

After intravenous administration in unpremedicated adult patients, 2 ml Sublimaze may be expected to provide sufficient analgesia for 10-20 minutes in surgical procedures involving low pain intensity. 10 ml Sublimaze injected as a bolus gives analgesia lasting about one hour. The analgesia produced is sufficient for surgery involving moderately painful procedures. Giving a dose of 50 mcg/kg Sublimaze will provide intense analgesia for some four to six hours, for intensely stimulating surgery.

Sublimaze may also be given as an infusion. In ventilated patients, a loading dose of Sublimaze may be given as a fast infusion of approximately 1 mcg/kg/min for the first 10 minutes followed by an infusion of approximately 0.1 mcg/kg/min. Alternatively the loading dose of Sublimaze may be given as a bolus. Infusion rates should be titrated to individual patient response; lower infusion rates may be adequate. Unless it is planned to ventilate post-operatively, the infusion should be terminated at about 40 minutes before the end of surgery.

Lower infusion rates, e.g. 0.05-0.08 mcg/kg/minute are necessary if spontaneous ventilation is to be maintained. Higher infusion rates (up to 3 mcg/kg/minute) have been used in cardiac surgery.

Sublimaze is chemically incompatible with the induction agents thiopentone and methohexitone because of wide differences in pH.

Child Dosage

Children

The usual dosage regimen in children is as follows:

Use in children:

Analgesia during operation, enhancement of anaesthesia with spontaneous respiration

Techniques that involve analgesia in a spontaneous breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique with experienced personnel in an environment that can manage sudden chest wall rigidity requiring intubation, or apnoea requiring airway support.

The usual dosage regimen is as follows:

Spontaneous respiration:

Child 2 years –12 years : initially 2–3 micrograms/kg, then 1 microgram/kg as required

Assisted ventilation:

Child 2 years –12 years : initially 2–3 micrograms/kg, then 1 microgram/kg as required

Elderly Dosage

Use in elderly and debilitated patients: It is wise to reduce the dosage in the elderly and debilitated patients. The effect of the initial dose should be taken into account in determining supplemental doses

Contra Indications

Respiratory depression, obstructive airways disease. Concurrent administration with monoamine oxidase inhibitors, or within 2 weeks of their discontinuation. Known intolerance to fentanyl or other morphinomimetics.

Special Precautions

Warnings:

Tolerance and dependence may occur. Following intravenous administration of fentanyl, a transient fall in blood pressure may occur, especially in hypovolaemic patients. Appropriate measures to maintain a stable arterial pressure should be taken.

Significant respiratory depression will occur following the administration of fentanyl in doses in excess of 200 mcg. This, and the other pharmacological effects of fentanyl, can be reversed by specific narcotic antagonists (e.g. naloxone). Additional doses of the latter may be necessary because the respiratory depression may last longer than the duration of action of the opioid antagonist.

Bradycardia and possibly asystole can occur in non-atropinised patients, and can be antagonised by atropine.

Muscular rigidity (morphine-like effect) may occur.

Rigidity, which may also involve the thoracic muscles, can be avoided by the following measures:

− slow IV injection (usually sufficient for lower doses);

− premedication with benzodiazepines;

− use of muscle relaxants.

Precautions:

Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway.

Techniques that involve analgesia in a spontaneous breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique with experienced personnel in an environment that can manage sudden chest wall rigidity requiring intubation, or apnoea requiring airway support.

As with all opioid analgesics, care should be observed when administering fentanyl to patients with myasthenia gravis.

It is wise to reduce dosage in the elderly and debilitated patients.

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.

Administration in labour may cause respiratory depression in the new born infant.

As with all potent opioids, profound analgesia is accompanied by marked respiratory depression, which may persist into or recur in the early postoperative period. Care should be taken after large doses or infusions of fentanyl to ensure that adequate spontaneous breathing has been established and maintained before discharging the patient from the recovery area.

Resuscitation equipment and opioid antagonists should be readily available. Hyperventilation during anaesthesia may alter the patients response to CO₂, thus affecting respiration postoperatively.

The use of rapid bolus injections of opioids should be avoided in patients with compromised intracerebral compliance; in such patients the transient decrease in the mean arterial pressure has occasionally been accompanied by a transient reduction of the cerebral perfusion pressure.

Interactions

The use of opioid premedication, barbiturates, benzodiazepines, neuroleptics, halogenic gases and other non-selective CNS depressants (e.g. alcohol) may enhance or prolong the respiratory depression of fentanyl.

When patients have received CNS-depressants, the dose of fentanyl required will be less than usual. Likewise, following the administration of fentanyl the dose of other CNS depressant drugs should be reduced.

Fentanyl, a high clearance drug, is rapidly and extensively metabolised mainly by CYP3A4. Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of iv fentanyl.

Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds; however, peak plasma concentrations after a single dose of iv fentanyl were not affected.

When fentanyl is used in a single dose, the concomitant use of potent CYP3A4 inhibitors such as ritonavir requires special patient care and observation. With continuous treatment, dose reduction of fentanyl may be required to avoid accumulation of fentanyl, which may increase the risk of prolonged or delayed respiratory depression.

Bradycardia and possibly asystole can occur when fentanyl is combined with non-vagolytic muscle relaxants.

The concomitant use of droperidol can result in a higher incidence of hypotension.

Adverse Reactions

Adverse events reported in association with intravenous fentanyl use are listed below:

Central & Peripheral Nervous System Disorders

Common: Muscle rigidity (which may also involve the thoracic muscles), myoclonic movements, dizziness

Cardiovascular Disorders, General

Common: Hypotension

Heart Rate and Rhythm Disorders

Common: Bradycardia

Rarely: Asystole

Respiratory System Disorders

Common: Apnea, respiratory depression

Uncommon: Laryngospasm

Rarely: Secondary rebound respiratory depression

Gastro-Intestinal System Disorders

Very Common: Nausea, vomiting

Psychiatric Disorders

Very Rarely: Insomnia, sexual dysfunction (e.g. decreased libido)

Body as a Whole – General Disorders

Uncommon: Allergic reactions (such as anaphylaxis, bronchospasm, pruritus, urticaria)

When a neuroleptic is used with fentanyl, the following adverse reactions may be observed: chills and/or shivering, restlessness, post-operative hallucinatory episodes and extrapyramidal symptoms.

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