DBL™ Fentanyl

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Fentanyl citrate 78.125 µg/mL equivalent to 50 µg/mL fentanyl; Fentanyl citrate 78.125 µg/mL
Available from:
Pfizer New Zealand Limited
INN (International Name):
Fentanyl citrate 78.125 µg/mL (equivalent to 50 µg/mL fentanyl)
Dosage:
50 mcg/mL
Pharmaceutical form:
Solution for injection
Composition:
Active: Fentanyl citrate 78.125 µg/mL equivalent to 50 µg/mL fentanyl Excipient: Water for injection Active: Fentanyl citrate 78.125 µg/mL Excipient: Hydrochloric acid Sodium chloride Sodium hydroxide Water for injection
Units in package:
Ampoule, glass, 10mL, 5 dose units
Class:
Class B3 Controlled Drug
Prescription type:
Class B3 Controlled Drug
Manufactured by:
Macfarlan Smith Ltd
Product summary:
Package - Contents - Shelf Life: Ampoule, glass, 10mL - 5 dose units - 24 months from date of manufacture stored at or below 25°C protect from light - Ampoule, glass, 2mL - 5 dose units - 24 months from date of manufacture stored at or below 25°C protect from light
Authorization number:
TT50-4461
Authorization date:
1990-10-17

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

DBL

FENTANYL INJECTION

1. Product name

Fentanyl citrate

2. Qualitative and quantitative

composition

It is presented in ampoules and containing 2 mL or 10 mL of a 50 microgram per mL solution of fentanyl

present as fentanyl citrate. The pH of the solution is adjusted to between 4.0 to 7.5, if necessary

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Fentanyl Injection is a sterile solution of fentanyl citrate in water for injections.

4. Clinical particulars

4.1 Therapeutic indications

DBL Fentanyl Injection is indicated for:

analgesic

action

short

duration

during

anaesthetic

periods,

premedication,

induction

maintenance, and in the immediate post-operative period (recovery room) as the need arises;

use as a narcotic analgesic supplement in general and regional anaesthesia;

administration with a neuroleptic such as droperidol injection as an anaesthetic premedication, for the

induction of anaesthesia, and as an adjunct in the maintenance of general and regional anaesthesia.

4.2 Dose and method of administration

Dosage should be individualised. Some of the factors to be considered in determining the dose are: age,

body

weight,

physical

status,

underlying

pathological

condition,

other

medicines,

type

anaesthesia to be used, and the surgical procedure involved.

The initial dose should be reduced in the elderly and in debilitated patients. The effect of the initial dose

should be taken into account in determining supplemental doses.

Vital signs should be monitored routinely.

Usual Dosage in Adult

1.

Premedication (To be appropriately modified in the elderly, debilitated and those who have received

other depressant medicines) 50 to 100 micrograms (1 to 2 mL) may be administered intramuscularly

30 to 60 minutes prior to surgery.

2.

Adjunct to general anaesthesia

Induction - 50 to 100 micrograms (1 to 2 mL) may be administered initially intravenously and

may be repeated at 2 to 3 minute intervals until the desired effect is achieved. A reduced dose as

low as 25 to 50 micrograms (0.5 to 1 mL) is recommended in elderly and poor-risk patients.

Maintenance - 25 to 50 micrograms (0.5 to 1 mL) may be administered intravenously or

intramuscularly

when

movement

and/or

changes

vital

signs

indicate

surgical

stress

lightening of analgesia.

3.

Adjunct to regional anaesthesia

50 to 100 micrograms (1 to 2 mL) may be administered intramuscularly or slowly intravenously

when additional analgesia is required.

4.

Post-operatively - (Recovery room)

50 to 100 micrograms (1 to 2 mL) may be administered intramuscularly for the control of pain,

tachypnoea, and emergence delirium. The dose may be repeated in one or two hours as needed.

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

Usual Dosage in Children

For induction and maintenance in children 2-12 years of age, a reduced dose as low as 20 to 30

micrograms (0.4 to 0.6 mL) per 10 kg is recommended.

(See section 4.4 Special warnings and precautions for use for use of DBL Fentanyl Injection with other

CNS depressants and in patients with altered response

4.3 Contraindications

DBL Fentanyl Injection is contraindicated in patients with known intolerance to fentanyl, any of the

components of DBL Fentanyl Injection or other morphinomimetics.

Fentanyl Injection should not be administered to children two years of age or younger, because safe

conditions for use have not been established. (See section 4.4 Special warnings and precautions for

use - Use in children) DBL Fentanyl Injection should not be administered to patients suffering from

bronchial asthma. As for any narcotic analgesic, it should not be used in patients who may be particularly

susceptible to respiratory depression, such as comatose patients who may have a head injury or brain

tumour. (See section 4.4 Special warnings and precautions for use). Severe and unpredictable

potentiation by MAO inhibitors has been reported with narcotic analgesics.

There is no evidence that fentanyl is potentiated by MAO inhibitors, but since such potentiation is found

with other narcotic analgesics, the use of DBL Fentanyl Injection in patients who have received MAO

inhibitors within 14 days is not recommended. (See section 4.5 Interactions with other medicines and

other forms of interaction).

DBL Fentanyl Injection may cause thoracic muscle rigidity upon intravenous administration. Therefore,

the need for reversal with muscle relaxants contraindicates its use in patients with a history of myasthenia

gravis.

4.4 Special warnings and precautions for use

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of

fentanyl with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics,

anxiolytics, tranquilizers, muscle relaxants, general anaesthetics, medicines with antihistamine-sedating

actions such as antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant

prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines

increases the risk of medicine-related mortality compared to use of opioid analgesics alone. Because of

similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other

CNS depressant drugs with opioid analgesics (see Section 4.5 Interactions with other medicines and

other forms of interaction).

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an

opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In

patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or

other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.

If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant,

prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow

patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when fentanyl

is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise

patients

drive

operate

heavy

machinery

until

effects

concomitant

benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance

use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death

associated with the use of additional CNS depressants including alcohol and illicit drugs (see Section 4.5

Interactions with other medicines and other forms of interaction).

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

Drug Dependence

DBL Fentanyl Injection can produce drug dependence of the morphine type and therefore has the

potential for being abused. DBL Fentanyl Injection may be habit forming.

Patients on chronic opioid therapy or with a history of opioid abuse may require higher doses.

Hypoventilation (Respiratory Depression)

Profound analgesia is accompanied by marked respiratory depression, which can persist or recur in the

post-operative period. Hyperventilation during anaesthesia may alter the patient's responses to CO

, thus

affecting respiration post-operatively. Therefore, patients should remain under appropriate surveillance.

DBL Fentanyl Injection should be used with caution in patients with severe impairment of pulmonary

function because of the possibility of respiratory depression, e.g. patients with chronic obstructive

pulmonary

disease,

patients

with

decreased

respiratory

reserve,

patient

with

potentially

compromised respiration. In such patients, narcotics may additionally decrease respiratory drive and

increase

airway

resistance.

During

anaesthesia,

this

managed

assisted

controlled

respiration.

Respiratory

depression

caused

narcotic

analgesics

reversed

narcotic

antagonists.

Appropriate surveillance should be maintained because the duration of respiratory depression of doses of

fentanyl employed during anaesthesia may be longer than the duration of narcotic antagonist action.

Consult individual prescribing information (naloxone) before employing narcotic antagonists. See also

discussion of narcotic antagonists in section 4.9 Overdose.)

Resuscitative equipment and a narcotic antagonist should be readily available to manage apnoea.

Muscle Rigidity

DBL Fentanyl Injection may cause muscle rigidity, particularly involving the muscles of respiration. This

effect is related to the speed of injection and its incidence can be reduced by a slow intravenous injection

(ordinarily sufficient for lower doses) premedication with

benzodiazepines

and the use

of muscle

relaxants.

Once the effect occurs, it is managed by the use of assisted or controlled respiration and, if necessary, by

a neuromuscular blocking agent compatible with the patient's condition.

Non-epileptic (myo)clonic movements can occur.

Head Injuries and Increased Intracranial Pressure

DBL Fentanyl Injection should be used with caution in patients who may be particularly susceptible to

respiratory depression, such as comatose patients who may have a head injury or brain tumour. In

addition, DBL Fentanyl Injection may obscure the clinical course of patients with a head injury.

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 short-lasting reduction of the cerebral perfusion pressure.

Cardiac Effects

Fentanyl Injection may produce bradycardia and possibly asystole if the patient has received an

insufficient amount of anticholinergic, or when DBL Fentanyl Injection is combined with non-vagolytic

muscle relaxants. Bradycardia may be treated with atropine. However, DBL

Fentanyl Injection should be

used with caution in patients with cardiac bradyarrhythmias.

Opioids may induce hypotension, especially in hypovolaemic patients. Appropriate measures to maintain

a stable arterial pressure should be taken.

Serotonin Syndrome

Co-administration of fentanyl with a serotonergic agent, such as a Selective Serotonin Re-uptake Inhibitor

(SSRI), a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor

(MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition.

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

Others

As has been observed with all narcotic analgesics, episodes suggestive of sphincter of Oddi spasm may

occur with DBL

Fentanyl Injection.

Opioids can cause central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the

risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the

opioid dosage using best practices for opioid taper.

Vital signs should be monitored carefully.

Use in Children

The safety of fentanyl citrate in children younger than two years of age has not been established.

Use in the Elderly or Debilitated Patients

It is recommended to reduce the dosage of DBL

Fentanyl Injection in the elderly and in debilitated

patients. Opioids should

be titrated

with caution

in patients

with any

of the following conditions:

uncontrolled hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism, impaired

hepatic or renal function. Such patients also require prolonged post-operative monitoring.

4.5 Interactions with other medicines and other forms of interaction

Medicines, such as, CNS depressants, barbiturates, benzodiazepines, neuroleptics, narcotics, alcohol

and general anaesthetics, will have additive or potentiating effects with fentanyl citrate.

When patients have received such medicines, the dose of DBL

Fentanyl Injection required will be less

than usual. Likewise, following the administration of DBL

Fentanyl Injection the dose of other CNS

depressant medicines should be reduced. Post-operative narcotics including DBL

Fentanyl Injection and

other depressants should be given initially in reduced doses, as low as 1/4 to 1/3 of those usually

recommended. As with other narcotics, the respiratory depressant effect of fentanyl citrate persists longer

than the measured analgesic effect. The total dose of all narcotic analgesics should be considered before

ordering narcotic analgesics during recovery from anaesthesia.

Certain forms of conduction anaesthesia, such as spinal anaesthesia and some peridural anaesthetics,

alter

respiration

blocking

intercostal

nerves.

Through

other

mechanisms

(see

section

Pharmacodynamics properties - Actions) fentanyl citrate can also alter respiration. Therefore, when

fentanyl citrate is used to supplement these forms of anaesthesia, the anaesthetist should be familiar with

the special properties of each medicine (particularly with the widely differing durations of actions), the

physiological alterations involved and be prepared to manage them in patients selected for these forms of

anaesthesia.

When fentanyl citrate is used with a neuroleptic such as droperidol, blood pressure may be altered and

hypotension can occur. If this occurs, the possibility of hypovolaemia should also be considered and

managed with appropriate parenteral fluid therapy. Repositioning the patient improves venous return to

the heart and should be considered when operative conditions permit. Care should be exercised in

moving and positioning patients because of the possibility of orthostatic hypotension. If volume expansion

with fluids together with other countermeasures do not correct hypotension, the administration of pressor

agents other than adrenaline should be considered. Because of the alpha-adrenergic blocking action of

droperidol, adrenaline may paradoxically decrease the blood pressure in patients treated with droperidol.

Pulmonary arterial pressure may also be decreased. This should be considered when interpreting

pulmonary arterial pressure measurements as it might determine the final management of the patient.

When droperidol is used with fentanyl citrate and the EEG is used for post-operative monitoring, it may be

found that the EEG pattern returns to normal slowly.

Nitrous oxide has been reported to produce cardiovascular depression when given with high doses of

fentanyl.

Profound bradycardia, sinus arrest and hypotension have occurred when patients receiving amiodarone

have been given fentanyl for anaesthesia.

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

Severe and unpredictable potentiation by MAO inhibitors has been reported with narcotic analgesics.

Since the safety of fentanyl in this regard has not been established, the use of DBL

Fentanyl Injection in

patients who have received MAO inhibitors within 14 days is not recommended.

Benzodiazepines and other Central Nervous System (CNS) Depressants

Clinical Impact

Due to additive pharmacologic effect, the concomitant use of benzodiazepines

or other CNS depressants including alcohol, increases the risk of respiratory

depression, profound sedation, coma, and death.

Intervention

Reserve concomitant prescribing of these drugs for use in patients for whom

alternative treatment options are inadequate. Limit dosages and durations to

minimum

required.

patients

closely

signs

respiratory

depression and sedation (see Section 4.4 Special warnings and precautions

for use).

Examples

Benzodiazepines

other

sedatives/hypnotics,

anxiolytics,

tranquilizers,

muscle

relaxants,

general

anaesthetics,

drugs

with

antihistamine-sedating

actions such as antipsychotics, other opioids, alcohol.

Caution

advised

when

fentanyl

co-administered

with

drugs

that

affect

serotonergic

neurotransmitter systems. The development of a potentially life-threatening serotonin syndrome may

occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors

(SSRIs),

Serotonin

Norepinephrine

Re-uptake

Inhibitors

(SNRIs),

with

drugs

which

impair

metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the

recommended

dose.

Serotonin

syndrome

include

mental-status

changes

(e.g.,

agitation,

hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia),

neuromuscular

abnormalities

(e.g.,

hyperreflexia,

incoordination,

rigidity),

and/or

gastrointestinal

symptoms (e.g., nausea, vomiting, diarrhoea). If serotonin syndrome is suspected, rapid discontinuation

of fentanyl should be considered.

Fentanyl is metabolised mainly via the human cytochrome P450 3A4 enzyme. It is a high clearance

medicine which is rapidly and extensively metabolised. Oral administration of itraconazole (a potent

inhibitor of CYP 3A4) at 200 mg/day given orally for 4 days did not have a statistically 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, after a single dose of IV fentanyl, the peak plasma concentrations 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. When fentanyl is given continuously with these

medicines, a reduction in the dose of fentanyl may be required. This will avoid the accumulation of

fentanyl and hence reduces the risk of prolonged or delayed respiratory depression.

There are no data on the in vivo interactions between fentanyl and other medicines inhibiting CYP 3A4

(eg ketoconazole, erythromycin, diltiazem and cimetidine).

4.6 Fertility, pregnancy and lactation

Pregnancy Category C. Although no teratogenic or acute embryotoxic effects have been observed in

animal experiments, insufficient data are available to evaluate any harmful effects in man. Consequently,

risks and potential benefits should be considered before this medicine is administered to pregnant

patients.

Administration (I.M. or I.V.) during childbirth (including caesarean section) is not recommended because

fentanyl crosses the placenta and because the foetal respiratory centre is particularly sensitive to opiates.

If fentanyl is nevertheless administered, an antidote for the child should always be at hand.

Fentanyl may enter the maternal milk. Therefore, breastfeeding is not recommended for 24 hours

following the administration of this medicine.

4.7

Effects on ability to drive and use machines

Patients should only drive or operate a machine if sufficient time has elapsed after the administration of

Fentanyl Injection.

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

4.8 Undesirable effects

As with other narcotic analgesics, the most common serious adverse reactions reported to occur with

fentanyl citrate are respiratory depression, apnoea, muscular rigidity (which may also involve the thoracic

muscles), myoclonic movements, and bradycardia.

If these remain untreated, respiratory arrest, circulatory depression, or cardiac arrest could occur.

Respiratory depression is more likely to occur with intravenous administration if a dose is given too

rapidly and it rarely occurs with intramuscular administration. If respiratory depression occurs during

anaesthesia,

assisted

controlled

respiration

will

provide

adequate

ventilation

without

reversing

analgesia.

Respiratory depression can be immediately reversed by narcotic antagonists (naloxone) which, it should

be noted, will also reverse analgesia.

Muscular rigidity is a common side effect and in some instances may be associated with reduced

pulmonary compliance and/or apnoea, laryngospasm and bronchospasm. Prompt reversal of this effect

can be achieved with the intravenous administration of an appropriate single dose of a muscle relaxant

such as succinylcholine. Assisted or controlled respiration is required to provide ventilation after the use

of muscle relaxants. Bradycardia and other cholinergic effects may occur, and can be controlled with an

appropriate

dose

atropine.

inclusion

atropine

other

anticholinergic

agents

preanaesthetic regimen tends to reduce the occurrence of such effects.

Other adverse reactions that have been reported are hypotension, dizziness, blurred vision, nausea,

emesis, laryngospasm, diaphoresis, itching and euphoria.

When a neuroleptic such as droperidol is used with DBL

Fentanyl Injection, the following adverse

reactions can occur: chills and/or shivering, restlessness, and post-operative hallucinatory episodes

sometimes

associated

with

transient

periods

mental

depression,

extrapyramidal

symptoms

(dystonia,

akathisia,

oculogyric

crisis)

have

been

observed

hours

post-operatively.

Extrapyramidal

symptoms

usually

controlled

with

anti-Parkinson

agents.

Post-operative

drowsiness is also frequently reported following the use of droperidol.

Elevated

blood

pressure

with

without

pre-existing

hypertension,

been

reported

following

administration of fentanyl citrate combined with droperidol. This might be due to unexplained alterations in

sympathetic activity following large doses. However, it is also frequently attributed to anaesthetic and

surgical stimulation during light anaesthesia.

Allergic reactions (such as anaphylaxis, bronchospasm, pruritis, urticaria) and asystole have been

reported. Since several medicines were co-administered during anaesthesia, it is uncertain whether there

is a causal relationship to fentanyl citrate.

Secondary rebound respiratory depression after the operation has been observed in rare instances.

4.9 Overdose

Symptoms

The manifestations of fentanyl citrate overdosage are an extension of its pharmacological actions. In

sufficient overdosage, fentanyl would produce narcosis, which may be preceded by marked skeletal

muscle rigidity. Cardio-respiratory depression accompanied by cyanosis occurs, followed by a fall in body

temperature, circulatory collapse, coma and death.

Treatment

In the presence of hypoventilation or apnoea, oxygen should be administered and respiration should be

assisted or controlled as indicated. A patent airway must be maintained. An oropharyngeal airway or

endotracheal tube might be indicated. If depressed respiration is associated with muscular rigidity, an

intravenous

neuromuscular

blocking

agent

might

required

facilitate

assisted

controlled

respiration.

A specific narcotic antagonist, such as naloxone, should be available for use as indicated to manage

respiratory depression. This does not preclude the use of more immediate countermeasures. The

duration of respiratory depression following overdosage of fentanyl may be longer than the duration of

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

narcotic antagonist action. Consult the package insert of the individual narcotic antagonists for details

about use. The patient should be carefully observed for 24 hours. Body warmth and adequate fluid intake

should be maintained. If hypotension occurs, and is severe or persists, the possibility of hypovolaemia

should be considered and managed with appropriate parenteral fluid therapy.

5 Pharmacological properties

5.1 Pharmacodynamics properties

Mechanism of action

Fentanyl is a potent narcotic analgesic with a rapid onset and short duration of action. The principal

actions of therapeutic value are analgesia and sedation. At a dose of 100 micrograms (2 mL), the

analgesic activity of fentanyl is approximately equivalent to 10 mg of morphine or 75 mg of pethidine.

Fentanyl differs from morphine by its short duration of analgesic activity, lack of emetic activity, and

minimal hypotensive activity.

The action of fentanyl is qualitatively similar to those of morphine and pethidine, i.e. analgesia, euphoria,

miosis, bradycardia, respiratory depression, bronchoconstriction, muscle rigidity and suppression of

cough reflexes. These effects can be reversed by specific narcotic antagonists, e.g. naloxone. As with

morphine, fentanyl-induced bradycardia from vagal stimulation is blocked or reversed by atropine.

Alterations in respiratory rate and alveolar ventilation, associated with narcotic analgesics may last longer

than the analgesic effect. As the dose of the narcotic is increased, the decrease in pulmonary exchange

becomes greater. Larger doses may produce apnoea. The behavioural effects in mice of fentanyl and

morphine are similar, and with toxic doses death is due to respiratory depression. The respiratory

depressant properties of fentanyl appear to be due to a central effect by decreasing the sensitivity of the

respiratory centre to carbon dioxide. In an experiment in cats, no effect on neuromuscular transmission

was observed in the presence of severe respiratory depression.

5.2 Pharmacokinetic properties

The onset of action of fentanyl is almost immediate when the medicine is given intravenously. However,

the maximal analgesic and respiratory depressant effect may not be noted for several minutes. The usual

duration of action of analgesic effect is 30 to 60 minutes after a single I.V. dose of up to 100 micrograms.

Following intramuscular administration, the onset of action is from 7 to 8 minutes and the duration of

action is 1 to 2 hours.

As with longer acting narcotic analgesics, the duration of the respiratory depressant effect of fentanyl may

be longer than the analgesic effect. The following observations have been reported concerning altered

respiratory response to CO

stimulation following administration of fentanyl to man:

1. Diminished sensitivity to co

stimulation may persist longer than depression of respiratory rate.

Fentanyl frequently slows the respiratory rate, but this effect is seldom noted for longer than 30

minutes regardless of the dose administered.

2. Altered sensitivity to CO

stimulation has been demonstrated for up to four hours following a single

intravenous dose of 600 micrograms (12 mL) fentanyl to healthy volunteers.

3.Duration and degree of respiratory depression is dose-related.

4.The peak respiratory depressant effect of a single intravenous dose of fentanyl is noted 5 to 15 minutes

following injection.

(See also section 4.4 Special warnings and precautions for use concerning respiratory depression.)

Fentanyl produces a minimum of cortical depression, and it is suggested that it exerts its action by filling

receptor sites located in the thalamus, mid-brain, and spinal cord. A specific narcotic antagonist, e.g.

naloxone, produces reversal of respiratory, cardiovascular, miotic, and motor incoordination effects, as

well as analgesia, euphoria, and sedation. Rigidity of the diaphragm and intercostal muscles can be

eliminated by succinylcholine. Cholinergic effects, e.g. bradycardia, are reversed by atropine.

Fentanyl is metabolised primarily in the liver. In humans, in vitro experiments have demonstrated that

fentanyl is metabolised mainly by cytochrome P450 3A4 (CYP 3A4) to norfentanyl via oxidative N-

dealkylation.

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

5.3 Preclinical safety data

Histamine assays and skin wheal testing in man, as well as in vivo testing in dogs, indicate that histamine

release rarely occurs with fentanyl. Experiments in dogs, have shown that intravenously administered

fentanyl at doses 2-4 times the recommended human dose, had minimal effect on blood pressure and

heart rate. Much higher doses of fentanyl citrate, ranging from 100-400 micrograms/kg, produce an

immediate fall in blood pressure, followed by partial recovery, and a sustained hypotensive effect lasting

up to 30 minutes.

6. Pharmaceutical particulars

6.1 List of excipients

Hydrochloric acid

Sodium chloride

Sodium hydroxide

Water for injection

The solution does not contain any preservative.

6.2 Incompatibilities

Fentanyl is incompatible with thiopentone sodium and methohexitone sodium.

6.3 Shelf life

24 months from date of manufacture stored at or below 25°C protect from light

6.4 Special precautions for storage

Store below 25

C. Protect from light.

6.5 Nature and contents of container

Package quantities

Strength

Packs

100 micrograms per 2 mL

5 x 2 mL Ampoules glass

500 micrograms per 10 mL

5 x 10 mL Ampoules glass

6.6 Special precautions for disposal and other handling

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue. Any

unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Medicine schedule

Class B3 Controlled Drug

8. Sponsor

Toll Free Number: 0800 736 363

9. Date of first approval

October 1990

Pfizer New Zealand Limited

PO Box 3998

Auckland, New Zealand

Data Sheet – New Zealand

Version: pfdfenti10120

Supercedes: version 5.0

10. Date of revision of the text

January 2020

Summary table of changes

Section changed

Summary of new information

Addition of text regarding central sleep apnoea and sleep-related hypoxemia.

Similar products

Search alerts related to this product

Share this information