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ALFENTANIL 500 MICROGRAMS/ML SOLUTION FOR INJECTION

Active substance(s): ALFENTANIL HYDROCHLORIDE

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TECHNICAL LEAFLET

D00643

Alfentanil 500 micrograms/ml Solution for Injection
Alfentanil 500 micrograms/ml Solution for Injection contains
alfentanil hydrochloride equivalent to 500 micrograms alfentanil
base per ml. The solution is supplied in clear glass ampoules
containing either 1mg of alfentanil base in 2ml or 5mg of alfentanil
base in 10ml or in vials containing 25mg of alfentanil base in 50ml.

Special warnings and precautions for use

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warnings:
Following administration of Alfentanil 500 micrograms/ml
Solution for Injection, a transient 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.

Therapeutic Indications: As an analgesic supplement for use
before and during anaesthesia. It is indicated for:
1. Short procedures and outpatient surgery
2. Procedures of medium and long duration when given as a bolus
followed by supplemental doses or by continuous infusion.
At very high doses, alfentanil may be used as an anaesthetic
induction agent in ventilated patients

Significant respiratory depression will occur following
administration of Alfentanil 500 micrograms/ml Solution for
Injection in doses in excess of 1mg and is dose related. This and
the other pharmacological effects of Alfentanil 500
micrograms/ml Solution for Injection are usually of short duration
and can be reversed by specific opioid antagonists (e.g. Naloxone).
Additional doses of the antagonists may be necessary because the
respiratory depression may last longer than the duration of action
of the opioid antagonist.

Posology and Method of Administration: For Intravenous
administration. Alfentanil 500 micrograms/ml Solution for
Injection by the intravenous route can be administered to both
adults and children. The dosage of Alfentanil 500 micrograms/ml
Solution for Injection should be individualised according to age,
bodyweight, physical status, underlying pathological condition,
use of other drugs and type of surgery and anaesthesia.
The usual recommended dosage regimen is as follows:

Like other opioids, alfentanil may cause bradycardia, an effect that
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 occur, appropriate measures should be instituted.

Clinical Particulars

Initial

Supplemental

Adults
Spontaneous
respiration
500 micrograms (1ml) 250 micrograms (0.5ml)
Assisted ventilation 30-50 micrograms /kg 15 micrograms/kg
Children
Assisted ventilation 30-50 micrograms/kg

15 micrograms/kg

If desired, Alfentanil 500 micrograms/ml Solution for Injection can
be mixed with Sodium Chloride Injection BP, Dextrose Injection BP
or Compound Sodium Lactate Injection BP (Hartmann’s solution).
Such dilutions are compatible with plastic bags and giving sets.
These dilutions should be used within 24 hours of preparation.
Use in children: Children may require higher or more frequent
dosing owing to a shorter half-life of alfentanil in this age group.
Use in elderly and debilitated patients: Lower or less frequent dosing
may be required owing to a longer half-life of alfentanil (dilution may
be helpful).
In spontaneously breathing patients, the initial bolus dose should
be given slowly over about 30 seconds (dilution may be helpful).
After intravenous administration in unpremedicated adult
patients, 1ml of Alfentanil 500 micrograms/ml Solution for
Injection may be expected to have a peak effect in 90 seconds and
to provide analgesia for 5-10 minutes. Periods of more painful
stimuli may be overcome by the use of small increments of
alfentanil. For procedures of longer duration, additional
increments will be required.
In ventilated patients, the last dose of alfentanil should not be given
later than about 10 minutes before the end of surgery to avoid the
continuation of respiratory depression after surgery is complete.
In ventilated patients undergoing longer procedures, alfentanil
may be infused at a rate of 0.5 - 1.0 micrograms/kg/minute.
Adequate plasma concentrations of alfentanil will only be
achieved rapidly if this infusion is preceded by a loading dose of
50-100 micrograms/kg, given as a bolus or fast infusion over 10
minutes. Even lower doses may be adequate, for example, in
geriatric patients or where anaesthesia is being supplemented by
other agents. The infusion should be discontinued up to 30
minutes before the anticipated end of surgery. Increasing the
infusion rate may prolong recovery. Therefore supplementation of
the anaesthetic, if required, is best managed by extra bolus doses
of Alfentanil 500 micrograms/ml Solution for Injection (1-2ml) or
low concentrations of a volatile agent for brief periods.
Patients with severe burns presenting for dressing, etc, have
received a loading dose of 18-28 micrograms/kg/min for up to 30
minutes without requiring mechanical ventilation. In heart
surgery, when used as a sole anaesthetic, doses in the range of
12-50 mg/hour have been used.
Contra-indications


Obstructive airways 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 Caesarean section due to the possibility of respiratory
depression in the new-born infant.



Patients with a known intolerance to alfentanil or other
morphinomimetics.

Asystole 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.

D00643

Alfentanil 500 micrograms/ml
Solution for Injection
Alfentanil hydrochloride
(Referred to as Alfentanil Injection in this leaflet)
Read all of this leaflet carefully before you are given this
medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If any of the side effects gets serious, or if you notice any side
effects not listed in this leaflet, please tell your doctor or nurse.
1.
2.
3.
4.
5.
6.

What Alfentanil Injection is and what it is used for
Before you are given Alfentanil Injection
How Alfentanil Injection will be given
Possible side effects
How to store Alfentanil Injection
Further information

1. What Alfentanil Injection is and what it is
used for
Alfentanil belongs to a group of medicines called opioid
analgesics, which are used as painkillers before and during
anaesthesia.
Alfentanil Injection is used to relieve pain during both short and
long surgical procedures. In very large doses it may also be used to
induce anaesthesia.

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

You should not be given Alfentanil Injection if you:
• are allergic (hypersensitive) to alfentanil hydrochloride or to
any of the other ingredients listed in section 6 of this leaflet
• suffer from breathing difficulties
• are taking or have recently taken in the last 2 weeks any
drugs used to treat depresion known as monoamine oxidase
inhibitors (MAOI’s)
• are in labour
• are dependent on alfentanil or any other opioid drugs

As with all opioids, profound analgesia is accompanied by marked
respiratory depression, which may persist into or recur in the early
post-operative period. Care should be taken after infusions or
large doses of alfentanil to ensure that adequate spontaneous
breathing has been established and maintained in the absence of
stimulation before discharging the patient from the recovery area.
Resuscitation equipment and narcotic antagonists should be
readily available. Hyperventilation during anaesthesia may alter
the patient’s response to carbon dioxide, thus affecting respiration
postoperatively.
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.
Interactions with other medical products and other forms of
interaction:
Alfentanil is metabolised mainly via the human cytochrome P450
3A4 enzyme. Available human pharmacokinetic data indicate that
the metabolism of alfentanil may be inhibited by Fluconazole,
Erythromycin, Diltiazem and Cimetidine (known cytochrome P450
3A4 enzyme inhibitors).
In vitro data suggest that other potent cytochrome P450 3A4
enzyme inhibitors (e.g. Ketoconazole, Itraconazole, Ritonavir) may
also inhibit the metabolism of alfentanil. 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 500 micrograms/ml Solution for Injection.
Treatment with drugs that may depress the heart or increase vagal
tone, such as beta-blockers and anaesthetic agents, may
predispose to bradycardia or hypotension. Bradycardia and
possibly asystole can occur when Alfentanil 500 micrograms/ml
Solution for Injection is combined with non-vagolytic muscle
relaxants.
The use of opioid premedication, barbiturates, benzodiazepines,
neuroleptics, halogenic gases and other non-selective CNS
depressants may enhance or prolong the respiratory depressant
effects of alfentanil.
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. Likewise, following the
Continued overleaf

Driving and using machines
This medicine can affect your ability to drive and operate
machinery. Do not drive or operate machinery if you feel drowsy
or cannot think clearly.
Having Alfentanil Injection with food and drink:
You are advised not to drink alcohol during your treatment with
this medicine.

In this leaflet:

Precautions:
It is wise to reduce the 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.

Alfentanil 500 micrograms/ml Solution for Injection may induce
muscle rigidity during induction. 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 a benzodiazepine;
- Administration of a muscle relaxant just prior to administration
of Alfentanil 500 micrograms/ml Solution for Injection
Non-epileptic myoclonic movements can occur.

Pregnancy and breast-feeding
If you are pregnant, trying to become pregnant, or are breastfeeding, please tell your doctor before being given Alfentanil
Injection. It is recommended that you should not be given
Alfentanil Injection if you are in labour or are breast-feeding.

2. Before you are given Alfentanil Injection

Take special care with Alfentanil Injection
Tell your doctor if you:
• are elderly or ill
• suffer from an underactive thyroid
• suffer from lung disease or any other breathing problems
• suffer from alcoholism
• suffer from liver or kidney problems
• are receiving opioid therapy or have a history of opioid abuse
• have suffered a head injury or are experiencing severe and
undiagnosed headaches
• have been told you are suffering from low blood volume. This
may happen if you have lost a lot of blood or are suffering from
severe dehydration.
If any of the above apply to you or your child please tell your
doctor.
Taking other medicines
Please tell your doctor or nurse if you are taking or have recently
taken any other medicines, including medicines obtained without
a prescription.
Alfentanil Injection should not be given with drugs used to treat
severe depression, such as phenelzine or moclobemide, or if you
are within 2 weeks of discontinuing them. These drugs are known
as Monoamine Oxidase Inhibitors (MAOIs).
Other medicines that may interact with Alfentanil Injection
include:
• fluconazole, itraconazole and ketoconazole, medicines used to
treat fungal infections
• erythromycin, a medicine used to treat bacterial infections
• diltiazem, a medicine used to treat chest pain and high blood
pressure
• cimetidine, a medicine used to treat stomach ulcers
• anaesthetics such as halogenic gases
• medicines used to relax your muscles
• other opioid medicines such as morphine
• medicines that make you feel sleepy such as barbiturates
• medicines used to treat mental disorders known as neuroleptics
• medicines used to treat anxiety known as benzodiazepines
• medicines used to treat high blood pressure (beta-blockers)
such as propranolol and atenolol
• ritonavir, a medicine used to treat HIV

3. How Alfentanil Injection will be given
This medicine is an injection and will be given to you by your
doctor. Your doctor will determine the dose you need depending
on your age, general health and the type of surgery to be
performed. Alfentanil Injection will be given to you into a vein
either by injection or infusion (drip).
Adults:
The usual dose for patients who can breathe on their own is 500
micrograms followed by 250 micrograms if needed.
The usual dose for patients whose breathing is being helped by a
machine (assisted ventilation) is 30-50 micrograms per kilogram of
body weight, followed by 15 micrograms per kilogram of body
weight if needed.
Children:
The usual dose for children whose breathing is being helped by a
machine (assisted ventilation) is 30-50 micrograms per kilogram of
body weight, followed by 15 micrograms per kilogram of body
weight if needed.
The elderly or ill:
You may be given smaller or less frequent doses than other adults.
If you are given too much of Alfentanil Injection
This medicine will be given to you in hospital so it is unlikely you
will receive too much. Your doctor has information on how to
recognise and treat an overdose.
If you feel unwell after being given this medicine, or are at all
concerned you have been given too much, tell your doctor or
nurse.

4. Possible side effects
Like all medicines, Alfentanil Injection can cause side effects,
although not everybody gets them.
Repeated use of alfentanil can result in tolerance and
addiction
If any of the following symptoms occur tell your doctor or nurse
immediately. These are symptoms of a serious allergic reaction.
• sudden wheeziness and tightness of chest
• swelling of eyelids, face or lips
• skin lumps or hives
• skin rash (red spots), itchiness, fever
• collapse
If any of the following symptoms occur tell your doctor or nurse
immediately. These are symptoms of a heart attack.
• sudden chest pains
• shortness of breath
• sweating
• anxiety
If you experience shallow breathing tell your doctor or nurse
immediately as this can lead to loss of consciousness.
Very common side effects may affect more than 1 in 10 people.
These include:
• feeling sick or being sick
Common side effects may affect between 1 and 10 patients out of
every 100. These include:
• high or low blood pressure
• muscle stiffness
• jerky movements
• dizziness
• fast or slow heartbeat
• feeling sleepy
• difficulty breathing

Continued overleaf

Uncommon side effects may affect 1 to 10 patients out of every
1000. These include:
• fainting, fits
• pinpoint pupils
• stopping breathing
• increased body temperature/fever
• pain at the injection site
• shivering
• headache
• an irregular heartbeat
• feeling disoriented or worried
• feeling ‘high’
• cough
• frequent problems in breathing
• hiccups
• itching
• sweating
• blurred or double vision

administration of alfentanil, the dose of other CNS depressant
drugs should be reduced.
Pregnancy and Lactation: 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, it is necessary to consider possible risks and
potential advantages before administering this drug to pregnant
patients.
Intravenous administration during childbirth (including caesarean
section) is not recommended, because alfentanil crosses the
placenta and because the foetal respiratory centre is particularly
sensitive to opiates. If, however, Alfentanil 500 micrograms/ml
Solution for Injection is administered, an antidote should always
be at hand for the child.
Alfentanil may appear in breast milk. It is therefore recommended
that breast feeding is not initiated within 24 hours of treatment.

If any of the side effects get serious, or if you notice any side
effects not listed in this leaflet, please tell your doctor or nurse.

Effects on the Ability to Drive and Use Machines: Where early
discharge is envisaged, patients should be advised not to drive or
operate machinery for 24 hours following administration.

5. How to store Alfentanil Injection

Other Undesirable Effects: Adverse events reported in
association with Alfentanil 0.5mg/ml Injection use in clinical trials
are listed below by decreasing frequency within each body system.
Frequency estimate: Very common>10%; Common>1% to <10%;
Uncommon>0.1% to <1%.

Keep out of the reach and sight of children.
You should not be given Alfentanil Injection after the expiry date
stated on the vial or ampoule and carton labels. The expiry date
refers to the last day of that month. The doctor or nurse will check
that the product has not passed this date.

Application Site Disorders
Uncommon: injection site pain, shivering
Isolated reports: pyrexia

Do not store above 25°C.

Body as a Whole – General Disorders
Uncommon: shivering, allergic reactions (such as anaphylaxis,
bronchospasm, urticaria)

6. Further Information
What Alfentanil Injection contains
Active ingredient: Alfentanil hydrochloride 545 microgram,
equivalent to 500 micrograms alfentanil base.
Other ingredients: sodium chloride, hydrochloric acid 10% and
water for injections.
What Alfentanil Injection looks like and contents of the pack
Alfentanil Injection is a clear, colourless solution supplied in clear
glass ampoules and vials. Each ampoule contains 2ml or 10ml of
the solution packed in packs of 10 and ach vial contains 50ml of
the solution packed as a single unit.
Marketing Authorisation Holder and Manufacturer
Martindale Pharmaceuticals Ltd
Bampton Road,
Harold Hill,
Romford,
Essex, RM3 8UG
United Kingdom

In man, alfentanil at therapeutic doses had no detrimental effects
on myocardial performance. The cardiovascular stability is
remarkable both in healthy and poor-risk patients. The only
changes seen in blood pressure and heart rate are transient, slight
decreases occurring immediately after induction. The incidence
and degree of respiratory depression is less and of shorter
duration after alfentanil than with fentanyl. Like other narcotic
analgesics, alfentanil increases the amplitude of the EEG and
reduces its frequency. Alfentanil reduces intraocular pressure by
about 45%. It blocks increases in plasma cortisol and in plasma
antidiuretic and growth hormones throughout surgery and
prevents increases in plasma catecholamines up to but not during
or after cardiopulmonary bypass in patients undergoing open
heart surgery.
Pharmacokinetic properties: After bolus injections ranging from
2.4 to 125 micrograms/kg, plasma levels in man decay
triexponentially with a terminal half life of approximately 90
minutes. Total distribution volume varies from 0.4 to 1.0 L/kg,
indicating a limited distribution of alfentanil to the tissues. Plasma
clearance, varying from 3.3 to 8.3 ml/kg/min represents
approximately one third of liver plasma flow indicating that
elimination of alfentanil is not flow dependent. Since only 0.4% of
the dose is excreted in the urine as unchanged drug, elimination
of alfentanil occurs mainly by metabolism.
These main parameters in patients undergoing surgery are similar
to those in healthy volunteers. Only when the drug was given as
the sole anaesthetic in a continuous high infusion over about 5
hours was the clearance of alfentanil reduced resulting in a plasma
half-life of about 200 minutes, the distribution volume not being
markedly changed.

Cardiovascular Disorders, General
Common: hypotension, hypertension

Plasma protein binding of alfentanil is 92%, mainly due to a strong
binding to the 'acute phase' α1 acid-glycoprotein. It is not bound
to the blood cells.

Central & Peripheral Nervous System Disorders
Common: muscle rigidity (which may also involve the thoracic
muscles), myoclonic movements, dizziness
Uncommon: headache
Isolated reports: loss of consciousness (postoperative period),
convulsion

Pharmacokinetics were comparable in rats, dogs and man. In
children, alfentanil has been shown to have a much shorter halflife than adults, whereas the elderly show a longer half-life for
alfentanil, after IV bolus doses.

Gastro-Intestinal System Disorders
Very Common: nausea, vomiting

List of Excipients: Sodium Chloride, Hydrochloric Acid 10%*,
Water for Injections, (* for pH adjustment only)

Heart Rate and Rhythm Disorders
Common: bradycardia, tachycardia
Uncommon: arrhythmia
Isolated reports: cardiac arrest

Incompatibilities: This medicinal product must not be mixed with
other medicinal products except those mentioned below.

Psychiatric Disorders
Common: somnolence
Uncommon: disorientation, agitation, euphoria
Respiratory System Disorders
Common: apnoea, respiratory depression
Uncommon: cough, recurrence of respiratory depression,
laryngospasm, hiccup
Isolated reports: Respiratory arrest (including fatal outcome)

This leaflet was last revised in: September 2008
Product licence number: PL 00156/0101

The onset of action of alfentanil is four times more rapid than
that of an equianalgesic dose of fentanyl. The peak analgesic and
respiratory depressant effects occur within 90 seconds.

Skin and Appendages Disorders
Uncommon: pruritus, sweating
Vision Disorders
Uncommon: blurred/double vision
Isolated reports: miosis or rapid eye movements
Overdose: The manifestations of alfentanil overdose are generally
an extension of its pharmacological action, which include the
following:
Bradycardia: Anticholinergics such as atropine or glycopyrrolate;
Hypoventilation or apnoea: Oxygen administration, assisted or
controlled respiration and an opioid antagonist may be required;
Muscle rigidity: Intravenous neuromuscular blocking agent may
be given.
If hypotension is severe or persists, the possibility of hypovolaemia
should be considered and controlled with appropriate parenteral
fluid administration.
The suggested treatments given above do not preclude the use of
other clinically indicated counter measures.

Pharmaceutical Particulars

Shelf Life: 2 years. From a microbiological point of view, the
diluted product should be used immediately. If not used
immediately, in-use storage times and conditions prior to use are
the responsibility of the user and would not normally be longer
than 24 hours at 2 to 8ºC, unless dilution has taken place in
controlled and validated aseptic conditions.
Special Precautions for Storage: Do not store above 25°C.
Nature and Contents of Container:
Clear Glass (Ph Eur Type 1) ampoules containing 1mg/2ml.
Clear Glass (Ph Eur Type 1) ampoules containing 5mg/10ml.
Clear Glass (Ph Eur Type 1) vials containing 25mg/50ml. The
closure of the vial consists of a bromobutyl rubber stopper with an
aluminium crimp seal.
The ampoules and vials are packed in a cardboard carton along
with a patient information leaflet.
Pack sizes:
10 x 2ml ampoules, 10 x 10ml ampoules, 1 x 50ml vials
Instruction for Use/Handling: Alfentanil 500micrograms/ml
Solution for Injection may be diluted with Sodium Chloride
Injection BP, Dextrose Injection BP or Compound Lactate BP
(Hartmann’s Solution).
Alfentanil 500 micrograms/ml Solution for Injection is for single
use only. Any unused product or contents or waste material
should be disposed of in accordance with local requirements.
Product licence number: PL 0156/0101
Prepared: August 2006
© Martindale Pharmaceuticals Ltd.

Body temperature and adequate fluid intake should be
maintained and the patient observed for 24 hours. A specific
opioid antagonist (e.g. naloxone) should be available to treat
respiratory depression.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties: Pharmacotherapeutic group:
Analgesics-Narcotics (opiod analgesic), ATC code: N01AH02
(alfentanil)
D00643

D00643

The analgesic potency of alfentanil is one quarter that of fentanyl.

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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