Alfentanil Piramal

Package leaflet: Information for the patient

ALFENTANIL PIRAMAL 0,5 mg/ml injection solution

alfentanil hydrochloride
Please read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What ALFENTANIL PIRAMAL is and what it is used for
2. What you need to know before taking ALFENTANIL PIRAMAL
3. How to take ALFENTANIL PIRAMAL
4. Possible side effects
5. How to store ALFENTANIL PIRAMAL
6. Contents of the pack and other information

1. What ALFENTANIL PIRAMAL is and what it is used for

ALFENTANIL PIRAMAL contains alfentanil hydrochloride, an opioid anesthetic medicine (numbs one or more parts of the body, prevents or relieves pain).

• ALFENTANIL PIRAMAL is indicated in adults for:
• induction of general anesthesia (a state of general body numbness with loss of consciousness) during surgical procedures;
• prevention or relief of pain during surgical procedures:
• of short duration in outpatient patients;
• of medium and long duration, in combination with other medicinal products to induce anesthesia.
• ALFENTANIL PIRAMAL is indicated in neonates, infants, and children under 18 years of age for prevention or relief of pain during short- and long-duration surgical procedures, in combination with other medicinal products to induce anesthesia.

2. What you need to know before taking ALFENTANIL PIRAMAL

ALFENTANIL PIRAMAL will not be administered to you or the child if:

• you are allergic to alfentanil hydrochloride or to any of the other ingredients of this medicine (listed in section 6);
• you are allergic to medicines similar to alfentanil hydrochloride (morphine-like medicines).

Warnings and precautions
This medicine is available only in hospital settings and will therefore be administered exclusively under the close supervision of qualified medical personnel.
Before ALFENTANIL PIRAMAL is administered to you or the child, inform the doctor:

• if you are being treated with sedative medicines (such as benzodiazepines or related drugs);
• if you have been long-term treated with medicines similar to ALFENTANIL PIRAMAL (other opioid medicines that interrupt or relieve pain) or have previously abused them;
• if you have uncontrolled hypothyroidism (a thyroid gland disorder causing swelling in the neck area);
• if you have lung disorders or breathing difficulties;
• if you have liver or kidney disease or a history of alcohol abuse;
• if you or a family member has previously suffered from alcohol, prescription medicine, or illegal substance abuse or dependence ("addiction");
• if you are a smoker;
• if you have previously experienced mood disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

This medicine contains alfentanil, which is an opioid medicine. Repeated use of opioid painkillers may reduce the drug's effectiveness (tolerance may develop). It may also lead to dependence and abuse, potentially resulting in a fatal overdose. If you are concerned about becoming dependent on ALFENTANIL PIRAMAL, it is important to consult your doctor.
Inform your doctor if you are pregnant, think you may be pregnant, or are breastfeeding (for further information, see section Pregnancy).
If you experience increased sensitivity to pain despite taking higher doses of the medicine (hyperalgesia), inform your doctor or pharmacist. Your doctor will assess whether the dosage should be adjusted or treatment discontinued.
In the period following surgery, you or the child may experience breathing problems and/or loss of consciousness; for this reason, the doctor will closely monitor you.
For athletes
Using this medicine without a therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.

Children and adolescents
ALFENTANIL PIRAMAL may cause breathing difficulties in newborns and very young children, which may be accompanied by muscle rigidity.
Therefore, during administration of ALFENTANIL PIRAMAL, the doctor will:

• carefully monitor the newborn's and/or child's respiratory function during and after surgery;
• consider administering a muscle relaxant simultaneously to prevent muscle rigidity.

Other medicines and ALFENTANIL PIRAMAL
Inform the doctor, nurse, or pharmacist if you/the child are taking, have recently taken, or might take any other medicine.
In particular, inform the doctor if you/the child are taking the following medicines.

Medicines that increase the effect of alfentanil
Taking the following medicines together with ALFENTANIL PIRAMAL may enhance the effects of ALFENTANIL PIRAMAL and consequently increase the risk of side effects, especially respiratory depression:

• monoamine oxidase inhibitors (medicines used to treat depression). The doctor may decide to discontinue these medicines before administering ALFENTANIL PIRAMAL. It is generally recommended to stop monoamine oxidase inhibitors at least two weeks before any surgical or anesthetic procedure.
• medicines that reduce/block the activity of the Central Nervous System, such as:
  • barbiturates (medicines that induce physical and mental relaxation and sleep; they also have anesthetic effects and may be used to treat epilepsy)
  • benzodiazepines (medicines similar to barbiturates, also used to treat anxiety)
  • neuroleptics (medicines used for mental disorders such as schizophrenia)
  • hypnotics (medicines that induce and maintain sleep)
  • halogenated gaseous anesthetics (a class of anesthetics). The doctor will reduce the dose of ALFENTANIL PIRAMAL to be administered during surgery and will also subsequently reduce the doses of the other medicines listed above.
• other medicines that affect the metabolism of ALFENTANIL PIRAMAL, for example:
  • ketoconazole, itraconazole, fluconazole, voriconazole (medicines used to treat fungal infections)
  • ritonavir (a medicine used to treat HIV)
  • erythromycin (an antibiotic)
  • diltiazem (a medicine used for heart problems and high blood pressure)
  • cimetidine (a medicine used for stomach ulcers). The doctor will provide special care and closely monitor you/the child and may reduce the dose of ALFENTANIL PIRAMAL to be administered during surgery.

In case of propofol use (a medicine used in hospitals to induce general anesthesia and sedation)
If propofol is used, the doctor may reduce the dose of ALFENTANIL PIRAMAL administered during surgery.
Concomitant use of ALFENTANIL PIRAMAL and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no other therapeutic options are available. The concomitant use of opioids and medicines used to treat epilepsy, nerve pain, or anxiety (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression, and may be fatal.
However, if your doctor prescribes ALFENTANIL PIRAMAL together with sedative medicines, the dose and duration of concomitant treatment should be limited.
Inform your doctor about all sedative medicines you are taking and strictly follow their dosage recommendations. It may be helpful to inform friends and family to watch for the symptoms listed above. Contact your doctor if these symptoms occur.

ALFENTANIL PIRAMAL and alcohol
Using ALFENTANIL PIRAMAL with alcoholic beverages may enhance the effect of ALFENTANIL PIRAMAL and cause respiratory depression.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before this medicine is administered.

Pregnancy
If you are pregnant, the doctor will administer this medicine only after carefully evaluating the potential risks and benefits.
Newborns of pregnant women treated with this medicine are at risk of developing neonatal abstinence syndrome (NAS).

Breastfeeding
Alfentanil may pass into breast milk; therefore, do not breastfeed within the first 24 hours immediately following administration of ALFENTANIL PIRAMAL.

Driving and using machines
ALFENTANIL PIRAMAL affects the ability to drive vehicles (including bicycles) and operate machinery for a certain period of time (this period may vary from 3–6 hours to 12–24 hours, depending on the dose of ALFENTANIL PIRAMAL administered).
Therefore, the doctor will decide when you/the child may resume driving (including bicycles) or using machinery after surgery. Until then, you and/or the child must not drive vehicles or operate machinery.

ALFENTANIL PIRAMAL 10 ml vial contains 35.4 mg of sodium (the main component of table/cooking salt) per 10 ml vial. This corresponds to 1.8% of the maximum daily recommended dietary intake of sodium for an adult.

3. How to take ALFENTANIL PIRAMAL

This medicine is available only in a hospital setting and will therefore be administered to you and/or the child exclusively under the close supervision of qualified medical personnel.
The most appropriate dose for you and/or the child will be determined by the doctor/anesthesiologist based on age, body weight, general condition, underlying disease, concomitant use of other medications being taken by you and/or the child, type of surgical procedure and type of anesthesia.
ALFENTANIL PIRAMAL will be administered to you and/or the child intravenously (via bolus injection or infusion).
ALFENTANIL PIRAMAL may be administered at any age.
If you and/or the child are given more ALFENTANIL PIRAMAL than prescribed
If an excessive dose of ALFENTANIL PIRAMAL is administered, you and/or the child may experience breathing difficulties up to respiratory depression, which may be associated with muscle rigidity and low blood pressure (hypotension).
In case an excessive dose of ALFENTANIL PIRAMAL is administered, the doctor will initiate appropriate supportive therapy.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The frequency and severity of the expected side effects in children are the same as those expected in adults,
except for mild to moderate muscle rigidity, which occurs mainly in children.
Based on clinical studies and post-marketing experience with the product, the following side effects may occur
during treatment with ALFENTANIL PIRAMAL:

Very common (may affect more than 1 in 10 people)

• nausea
• vomiting

Common (may affect up to 1 in 10 people)

• euphoria
• movement disorders
• dizziness
• physical and mental relaxation (sedation)
• difficulty in movement alternating with episodes of excessive motor activity (dyskinesia)
• visual disturbances
• reduced heart rate, i.e. number of heartbeats per minute (bradycardia)
• increased heart rate, i.e. number of heartbeats per minute (tachycardia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• decrease in blood pressure
• increase in blood pressure
• temporary cessation of breathing (apnea)
• muscle rigidity. Mild to moderate muscle rigidity occurs especially in children. Severe muscle rigidity and spasms may occur less frequently and may be accompanied by transient worsening of respiration, particularly with high doses of ALFENTANIL PIRAMAL or in cases of rapid infusion.
• fatigue
• chills
• pain at injection site
• procedural pain related to the surgical intervention

Uncommon (may affect up to 1 in 100 people)

• agitation
• crying
• headache
• somnolence
• poor response to external stimuli
• altered heart rhythm, i.e. irregular heartbeat (arrhythmia)
• decreased heart rate
• vein pain
• narrowing of the bronchi causing severe breathing difficulty due to reduced airflow (bronchospasm)
• hiccup
• increased levels of carbon dioxide in the blood, a metabolic waste product (hypercapnia)
• respiratory complication with contraction of throat muscles (laryngospasm)
• nosebleed (epistaxis)
• respiratory depression
• allergic skin rashes (allergic dermatitis)
• increased sweating (hyperhidrosis)
• itching
• pain
• confusion and postoperative agitation
• anesthesia-related respiratory complications
• anesthesia-related brain complications
• complications related to surgical procedures
• complications related to the insertion of a tube into the trachea, the passage starting from the throat down to the bronchi (endotracheal intubation)

Very rare (may affect up to 1 in 10,000 people)

• allergic reactions, including severe reactions (anaphylactic reactions)
• skin redness accompanied by itching (urticaria)
• disorientation
• postoperative loss of consciousness
• seizures
• involuntary contraction of one or more muscles (myoclonus)
• pupil constriction (miosis)
• heart attack (cardiac arrest)
• respiratory arrest
• respiratory depression, which may lead to death
• cough
• skin rashes (erythema, rash)
• increased body temperature (pyrexia)

Reporting of side effects
If you or the child experience any side effect, including those not listed in this leaflet, please contact your doctor. You may also report side effects directly via the national adverse reaction reporting system.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ALFENTANIL PIRAMAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after Exp. The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ALFENTANIL PIRAMAL contains

• The active substance is: alfentanil hydrochloride (each 10 ml vial contains 5.44 mg of alfentanil hydrochloride, equivalent to 5 mg of alfentanil).
• The other components are: sodium chloride (see section "ALFENTANIL PIRAMAL contains sodium"), water for injections.

Description of the appearance of ALFENTANIL PIRAMAL and package contents
ALFENTANIL PIRAMAL is a sterile aqueous solution for intravenous administration (via bolus injection or infusion). The solution is contained in 10 ml vials, packaged in boxes of 5 vials.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
PIRAMAL CRITICAL CARE ITALIA S.P.A.
Via XXIV Maggio 62/A, 37057 - San Giovanni Lupatoto - Verona (VR)
Manufacturer
Piramal Critical Care BV
Rouboslaan 32
2252 TR Voorschoten
The Netherlands

The following information is intended exclusively for physicians or healthcare professionals

SPECIAL WARNINGS
As with all potent opioids, respiratory depression is dose-dependent and can be reversed by specific antagonists (naloxone); however, repeated doses of naloxone or other opioid antagonists may be required, since respiratory depression may last longer than the duration of action of the opioid antagonist. Profound analgesia is associated with marked respiratory depression and loss of consciousness, which may persist or recur in the postoperative period. For these reasons, careful patient monitoring is essential, and resuscitation equipment and narcotic antagonist drugs must always be readily available. Hyperventilation during anesthesia may alter the patient's sensitivity to CO₂ and influence postoperative respiration.

Muscle rigidity, which may involve the thoracic muscles, can be prevented by the following measures: slow intravenous injection (generally sufficient for lower doses), premedication with benzodiazepines, and use of muscle relaxants.

Non-epileptic myoclonic movements may occur.

Bradycardia, and even cardiac arrest, may occur if the patient has received an insufficient dose of anticholinergic agent or if ALFENTANIL PIRAMAL is combined with non-vagolytic muscle relaxants. Bradycardia can be treated with atropine.

Opioids may cause arterial hypotension, especially in hypovolemic patients; therefore, appropriate measures should be taken to maintain stable arterial pressure.

Rapid bolus administration of opioids should be avoided in patients with impaired intracranial compliance; in such patients, a transient decrease in mean arterial pressure may occasionally be accompanied by a brief reduction in cerebral perfusion pressure.

Dosage reduction of ALFENTANIL PIRAMAL is recommended in elderly and debilitated patients.

Paediatric population
There is a higher risk of respiratory complications when alfentanil is administered to neonates and very young children compared to older children and adults. Therefore, younger paediatric patients must be closely monitored from the start of alfentanil administration.

Assisted ventilation equipment must be available for use in children of all ages, even for brief procedures in which the patient is breathing spontaneously.

In neonates and very young children treated with alfentanil, concomitant use of a muscle relaxant should be considered to prevent the risk of muscle rigidity. After completion of alfentanil treatment, all children must be monitored for a sufficient period to ensure that spontaneous respiration has been fully restored.

Due to variability in pharmacokinetic parameters, a lower dose of alfentanil may be required in neonates. Neonates must be closely monitored and the dose of alfentanil titrated according to response.

DOSAGE AND ADMINISTRATION SCHEDULE
ALFENTANIL PIRAMAL should be administered as an intravenous bolus for short surgical procedures, or as repeated boluses or continuous infusion for prolonged and painful surgical procedures.

The dosage of ALFENTANIL PIRAMAL must be individually determined based on age, body weight, general condition of the patient, underlying pathology, concomitant medications, type of surgical procedure and anesthetic technique. The drug may be administered to patients of any age.

Initial dose should be reduced in elderly and debilitated patients. The effect of the initial dose should be taken into account when determining supplemental doses.

To prevent bradycardia, a small intravenous (I.V.) dose of an anticholinergic agent may be administered just prior to induction of anesthesia. To prevent nausea and vomiting, droperidol may be administered.

1. Induction of anesthesia

An intravenous bolus dose equal to or greater than 120 μg/kg (17 ml/70 kg) induces hypnosis and
analgesia while maintaining good cardiovascular stability along with adequate muscle relaxation.

2. Short-duration and outpatient procedures

Small doses of ALFENTANIL PIRAMAL can be very useful in minor, short-duration surgical procedures with significant pain component, as well as in outpatient patients, provided that adequate monitoring equipment is available.
For procedures lasting less than 10 minutes, an intravenous bolus of 7–15 µg/kg (1–2 ml/70 kg) is used.
Slow injection of this dose (over 30 seconds) usually allows spontaneous respiration to be maintained.
For longer procedures, the bolus should be repeated every 10–15 minutes.
Spontaneous respiration may be maintained in many cases by slow injection of a dose ≤ 7 µg/kg (1 ml/70 kg); suggested increments with this technique are 3.5 µg/kg (0.5 ml/70 kg).
In outpatient procedures, it is preferable not to administer droperidol or benzodiazepines, as these drugs may prolong recovery times.
In this type of procedure, it is preferable to administer an anticholinergic, a short-acting hypnotic, ALFENTANIL PIRAMAL, and N₂O/O₂.
Any postoperative nausea that may occur is short-lived and easily controlled by conventional means.

3. Medium-duration procedures

The initial intravenous bolus dose should be adjusted according to the expected duration of the surgical procedure, according to the following scheme:

For procedures of longer duration or more aggressive type, analgesia can be maintained:

• either by additional doses of 15 µg/kg (2 ml/70 kg) of ALFENTANIL PIRAMAL as needed (to avoid the occurrence of postoperative respiratory depression, administration of the drug is not recommended during the last 10 minutes of the procedure);
• or by administration of ALFENTANIL PIRAMAL as a continuous infusion at a rate of 1 μg/kg/min (0.14 ml/70 kg/min) up to 5–10 minutes before the end of the procedure. Periods of higher surgical stimulus can be managed with small additional doses of ALFENTANIL PIRAMAL or by temporarily increasing the infusion rate. When ALFENTANIL PIRAMAL is used without concomitant administration of N\O/O\ or other inhalational anesthetics, a higher maintenance dose is required.

4. Long-duration procedures

ALFENTANIL PIRAMAL may be used as an analgesic component of anaesthesia in long-duration
surgical procedures, particularly when rapid extubation is required.
By adjusting the infusion rate according to the intensity of surgical stimulation and the patient's responsiveness,
optimal analgesia and stable autonomic conditions can be maintained.

Paediatric population
Assisted ventilation equipment must be available for use in children of all ages, even during short procedures
where the patient is breathing spontaneously.

Neonates (0–27 days): Pharmacokinetic parameters in neonates are highly variable, especially in preterm infants.
Clearance and plasma protein binding are low, so lower doses of alfentanil may be required. Neonates must be
closely monitored, and the dose of alfentanil should be titrated according to response.

Infants and young children (28 days–23 months): Clearance may be higher in this age group compared to adults.
To maintain analgesia, an increased infusion rate of alfentanil may be necessary.

Children (2–11 years): Clearance may be slightly higher, and an increased alfentanil infusion rate may be required.

Adolescents: Pharmacokinetic parameters of alfentanil in adolescents are similar to those in adults; therefore,
no specific dosage recommendations are needed for this patient group.

Dosage recommendations in the paediatric population
The wide variability in response to alfentanil makes it difficult to define precise dosage recommendations for younger children.
For older children, a bolus dose of 10 to 20 μg/kg of alfentanil for anaesthesia induction (e.g. to supplement propofol or inhalational anaesthesia) or as an analgesic is considered appropriate. Supplemental boluses of 5 to 10 μg/kg of alfentanil may be administered at appropriate intervals.

To maintain analgesia in children during surgery, an infusion rate of ALFENTANIL PIRAMAL of 0.5 to 2 μg/kg/min may be used.
The dose should be increased or decreased according to individual patient needs. When ALFENTANIL PIRAMAL is combined with an intravenous anaesthetic agent, the recommended dose is approximately 1 μg/kg/min.

USE DURING PREGNANCY
Intravenous administration of the drug during labour (including caesarean section) is not recommended, as alfentanil crosses the placental barrier and the newborn's respiratory centre is particularly sensitive to opioids. If ALFENTANIL PIRAMAL is nevertheless administered, assisted ventilation equipment must be immediately available for use in the newborn, if needed. An opioid antagonist must always be available for the newborn. The half-life of the opioid antagonist may be shorter than that of alfentanil; therefore, repeated administrations should be considered.

Chronic opioid use during pregnancy may lead to dependence in the newborn, resulting in neonatal abstinence syndrome (NAS). If prolonged opioid use during pregnancy is required, the patient should be informed of the risk of neonatal abstinence syndrome.

OVERDOSE
Signs and Symptoms
Overdose manifests as an exaggeration of the drug's pharmacological effects. Depending on individual sensitivity, the clinical picture is primarily characterized by the degree of respiratory depression, ranging from bradypnea to apnoea.

Treatment
In case of hypoventilation or apnoea, oxygen should be administered and respiration must be assisted and controlled as indicated. To reverse pharmacological depression, a specific opioid antagonist such as naloxone should be used according to its indications. This does not preclude the use of more immediate countermeasures. The duration of respiratory depression may exceed the duration of action of the opioid antagonist; therefore, additional doses of the antagonist may be required.

If respiratory depression is associated with muscle rigidity, administration of a neuromuscular blocker is recommended to facilitate controlled or assisted ventilation.

The patient must be closely monitored; body temperature and adequate fluid intake should be maintained. If hypotension is severe or persistent, hypovolaemia should be considered and, if present, corrected with appropriate parenteral fluid administration.