ALFENTANIL 500 MICROGRAMS / ML SOLUTION FOR INJECTION - patient leaflet, side effects, dosage

Patient leaflet - ALFENTANIL 500 MICROGRAMS / ML SOLUTION FOR INJECTION

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.

In this leaflet:

1. What Alfentanil Injection is and what it is used for

2. Before you are given Alfentanil Injection

3. How Alfentanil Injection will be given

4. Possible side effects

5. How to store Alfentanil Injection

6. 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.

2. Before you are given Alfentanil Injection

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

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

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.

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.

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

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.

5. how to store alfentanil injection

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.

Do not store above 25°C.

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

This leaflet was last revised in: September 2008

Product licence number: PL 00156/0101

MARTINDALE WTJe

Pharmaceuticals

Bampton Road, Harold Hill

Romford, RM3 8UG United Kingdom

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 breastfeeding is not initiated within 24 hours of treatment.

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.

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%.

Application Site Disorders

Uncommon: injection site pain, shivering

Isolated reports: pyrexia

Body as a Whole – General Disorders

Uncommon: shivering, allergic reactions (such as anaphylaxis, bronchospasm, urticaria)

Cardiovascular Disorders, General

Common: hypotension, hypertension

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

Isolated reports: loss of consciousness (postoperative period), convulsion

Gastro-Intestinal System Disorders

Very Common: nausea, vomiting

Heart Rate and Rhythm Disorders

Common: bradycardia, tachycardia

Uncommon: arrhythmia

Isolated reports: cardiac arrest

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)

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.

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)

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

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.

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

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.

Pharmaceutical Particulars

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

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

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 8°C, 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 EurType 1) ampoules containing 1mg/2ml. Clear Glass (Ph EurType 1) ampoules containing 5mg/10ml. Clear Glass (Ph EurType 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 × 2ml ampoules, 10×10ml ampoules, 1 × 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