Prospecto: information for the user

LIMIFEN 0.5 mg/ml injectable solution

Alfentanil

Read this prospectus carefully before starting to use this medicine, because it contains important information for you.

- Keep this prospectus, as you may need to read it again.

- If you have any doubts, consult your doctor or pharmacist.

- If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospectus. See section 4.

1.What is LIMIFEN 0.5 mg/ml injectable solution and for what it is used

2.What you need to know before starting to use LIMIFEN 0.5 mg/ml injectable solution

3.How to use LIMIFEN 0.5 mg/ml injectable solution

4.Possible adverse effects

5.Storage of LIMIFEN 0.5 mg/ml injectable solution

6.Contents of the package and additional information

What is LIMIFEN

LIMIFEN contains the active ingredient “alfentanil”.

What is LIMIFEN used for

LIMIFEN is a medication used for general anesthesia (making the patient sleep while undergoing an operation).

LIMIFEN is indicated for use in adults as:

Opioid analgesic in combination with other medications in regional anesthesia and in short or long duration interventions (administering new doses at certain times).

LIMIFEN is indicated for use in children of all ages including newborns as:

Opioid in association with a hypnotic to induce anesthesia, as opioid analgesic in association with general anesthesia and for short and long duration interventions.

No use LIMIFEN:

?if you have a known intolerance to alfentanilo or other opioids (medicines that have a similar effect to morphine)

Tenga especial cuidado con LIMIFEN:

Inform to your doctorif you have:

?lung diseases or breathing problems

?brain diseases

?thyroid problems

?liver or kidney problems

• You or any member of your family have abused alcohol or experienced dependence on it, prescription medications, or illegal drugs («addiction»).
• You smoke.
• You have ever had mood problems (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental health conditions.

This medicine contains alfentanilo, which is an opioid. Repeated use of opioid analgesics can make the drug less effective (the body gets used to it). It can also cause dependence and addiction, which can lead to a potentially fatal overdose. It is essential to consult your doctor if you are concerned about developing dependence on LIMIFEN.

LIMIFEN is a medication used for general anesthesia and should only be used by qualified individuals with medical skills.

Inform your doctor if you are pregnant, may become pregnant, or are breastfeeding (see the Pregnancy section for more information).

Inform your doctor or pharmacist if you have experienced an increase in pain sensitivity despite taking increasing doses (hyperalgesia). Your doctor will decide if you need to change the dose or stop taking this medication.

It is essential to note that LIMIFEN can weaken breathing. This can also occur after the operation. Therefore, you should be monitored for a period of time after the operation. Consult your doctor or nurse immediately if you experience intense drowsiness or breathing problems.

Use with food and drinks

Do not consume alcohol when using LIMIFEN as it can enhance the effects of this medication.

If you regularly consume alcohol, inform your doctor.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before taking a medication.

If you are pregnant or think you may be pregnant, consult your doctor, who will decide if you can use LIMIFEN.

LIMIFEN can be excreted in breast milk, so breastfeeding is not recommended until 24 hours after the last administration. Do not use breast milk that has been expressed within 24 hours of the last LIMIFEN administration.

If women receive this medication during pregnancy, there is a risk that the newborn may experience neonatal withdrawal syndrome.

Driving and operating machinery

LIMIFEN can decrease your alertness or affect your ability to drive vehicles. It is recommended to wait at least 24 hours after LIMIFEN administration before driving vehicles or using hazardous machinery.

Always seek advice from your doctor.

Information for athletes

It is reported to athletes that this medication contains a component that can establish a positive analytical result for doping control.

CNS depressants, alcohol, and other medications

Inform your doctor or pharmacist if you are taking, or have recently taken, any other medication, including over-the-counter medications or herbal remedies.Inform your doctor or pharmacist if you are taking any of the following medications as LIMIFEN may affect their proper functioning:

?Powerful analgesics, medications that affect the central nervous system (CNS depressants), especially medications known as benzodiazepines or related medications, alcohol, and some illegal drugs. If you are taking powerful analgesics or CNS depressants (e.g., sleeping pills, tranquilizers, medications for mental disorders, alcohol, some illegal drugs), inform your doctor because the LIMIFEN dose may need to be reduced. Additionally, if you receive a powerful analgesic or other CNS depressant after receiving LIMIFEN during surgery, it may be necessary to reduce the analgesic or other CNS depressant to reduce the risk of potentially severe side effects such as respiratory difficulties or shallow breathing, severe drowsiness, and decreased consciousness, coma, and death.The concomitant use of opioids and medications used to treat epilepsy, neurological pain, or anxiety (gabapentin and pregabalin) increases the risk of opioid overdose and respiratory depression and may put the patient's life at risk.

?Erythromycin (an antibiotic), cimetidine (a medication for stomach acid), or diltiazem (a medication used for a certain type of heart disease). These medications increase the effects of LIMIFEN; when such medications have been administered, the usual dose of LIMIFEN will be lower.

?Certain HIV medications (e.g., ritonavir) or certain medications for fungal infections (e.g., fluconazole, ketoconazole, itraconazole). It may be necessary to change the LIMIFEN dose.

• Medications for depression known as Monoamine Oxidase Inhibitors (MAOIs). It is not recommended to take these medications in the two weeks prior to or at the same time as LIMIFEN administration.
• Medications for depression known as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). Generally, it is not recommended to take these medications at the same time as LIMIFEN.

LIMIFEN injectable solution contains sodium

This medication contains 0.15 mmol (or 3.54 mg) of sodium per milliliter of solution. If you need large quantities of the solution (e.g., more than 6.5 milliliters, corresponding to more than 1 mmol of sodium), your doctor will take this into account if you have a sodium-controlled diet.

Children and adolescents

LIMIFEN can cause respiratory difficulties and muscle rigidity, especially in babies and very young children.

When LIMIFEN is administered to babies and young children:

Your breathing should be closely monitored during the operation and for some time after.

Your doctor may administer a muscle relaxant to prevent rigidity.

LIMIFEN contains sodium

LIMIFEN 2 ml ampoule: This medication contains less than 1 mmol of sodium (23 mg) per 2 ml ampoule, which is essentially "sodium-free".

LIMIFEN 10 ml ampoule: This medication contains 35.4 mg of sodium (main component of table salt) in each 10 ml ampoule. This corresponds to 1.8% of the maximum daily sodium intake recommended for an adult.

LIMIFEN is injected into a vein (intravenous use).

The amount of LIMIFEN depends on your situation. Your doctor will determine how much LIMIFEN you need based on your weight, age, and medical condition.

Use in children and adolescents

LIMIFEN is used with other medications (anesthetics or sedatives) in children and adolescents.

When LIMIFEN is administered as an injection with other medications such as anesthetics or to relieve pain in older children, the initial dose is usually 10 to 20 micrograms per kilogram of body weight. If additional injections are considered necessary, they may be administered at a dose of 5 to 10 micrograms per kilogram of body weight.

When LIMIFEN is administered as an infusion through a drip to maintain pain relief during a surgical procedure, the usual dose is 0.5 to 2 micrograms per kilogram of body weight per minute. If the LIMIFEN infusion through a drip is combined with an anesthetic, the usual dose is approximately 1 microgram per kilogram of body weight per minute.

In infants, LIMIFEN may be administered in lower and adjusted doses according to response.

In adolescents, LIMIFEN will be administered at doses similar to those administered in adults.

If you use more LIMIFEN than you should:

In the unlikely event of an overdose, your doctor will take necessary actions.

The primary symptom is difficulty breathing.

Information for the doctor in case of overdose

Immediate measures:

In case of hypoventilation or apnea, administer oxygen and control breathing.

A specific opioid antagonist should be used to control respiratory depression. Note that additional doses may be required.

Other measures:

If muscle rigidity accompanies respiratory depression, an intravenous neuromuscular blocking agent may be necessary.

If hypotension occurs or persists, consider possible hypovolemia and administer parenteral fluids accordingly.

The patient should be carefully monitored, and if necessary, provide appropriate supportive measures.

Like all medicines, LIMIFEN may cause side effects, although not everyone will experience them.

Very common:affect more than 1 in 10 people

Common:affect between 1 in 100 and 10 in 100 people

Uncommon:affect between 1 in 1,000 and 10 in 1,000 people

Rare:affect between 1 in 10,000 and 10 in 10,000 people

Very rare:affect less than 1 in 10,000 people

Unknown:the frequency cannot be estimated from available data

Very rare (affect less than 1 in 10,000 people):

• hypersensitivity (allergy) including anaphylactic reaction, anaphylactoid reaction, and urticaria
• disorientation
• loss of consciousness(postoperative period (after surgery)), convulsion, myoclonus (brief, involuntary contraction of muscles)
• miosis (pupil constriction)
• cardiac arrest
• respiratory arrest, respiratory depression (slow or inadequate breathing)(including fatal outcome), cough
• erythema (redness), rash (skin eruption)
• pyrexia (fever)

Other side effects that may occur include:

• abnormally slow and/or weak breathing or temporary interruption of breathing
• spasms of the respiratory and laryngeal tracts
• hypoxia
• irregular, slow, or rapid heart rhythm
• low or high blood pressure
• muscle stiffness or involuntary muscle movements, including slow movements, stiffness, or twitching
• dizziness
• nausea and vomiting.
• cardiac or respiratory arrest

• chills

• fatigue
• fever
• headache
• drowsiness
• lack of response to stimuli
• loss of consciousness
• convulsions
• agitation
• crying
• disorientation
• feeling of well-being or euphoria
• sedation
• nasal bleeding
• cough
• excessive carbon dioxide in the blood
• vision disturbance
• constricted pupils
• allergic dermatitis
• itching
• excessive sweating
• skin redness
• eruption.

Other complications that may occur include agitation postoperatively or confusion; respiratory or neurological complications; complications due to anesthesia or endotracheal intubation. You may experience pain, including at the injection site, vein, or pain due to the procedure.

Severe allergic reactions may occur in rare cases and may include:

• swelling of the face, lips, mouth, tongue, or throat
• difficulty swallowing or breathing
• skin eruption with itching (urticaria)

Possible side effects in children and adolescents

The frequency, type, and severity of side effects in children and adolescents are similar to those described above, with some exceptions. In newborns, mild or moderate muscle stiffness may occur frequently. Less frequently, there may be cases of severe stiffness and spasms accompanied by respiratory difficulty.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not appearing in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaramRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

This medication does not require special conditions for conservation.

Do not use LIMIFEN after the expiration date that appears on the packaging.

Composition of LIMIFEN0.5 mg/ml INJECTABLE SOLUTION

-LIMIFEN is a sterile, isotonic, preservative-free aqueous solution containing alfentanil.

Each milliliter of LIMIFEN contains 0.5 milligrams (mg) of alfentanil (as alfentanil hydrochloride) as the active ingredient.

The other components are sodium chloride and water for injection.

Aspect of the product and content of the package

LIMIFEN is presented in containers of 5 ampoules containing 2 milliliters or 10 milliliters.

Holder of the marketing authorization and responsible for manufacturing

Holder:

Piramal Critical Care B.V.

Rouboslaan 32, 2252 TR

Voorschoten

Netherlands

Responsible for manufacturing:Piramal Critical Care B.V.

Rouboslaan 32, 2252 TR

Voorschoten

Holland

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Euromed Pharma Spain S.L.

C/Eduard Maristany, 430-432

08918 Badalona

Barcelona - Spain

Last review date of this leaflet: August 2022

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals

Dosage and administration

LIMIFEN should be used as injections in bolus (in short-duration interventions) or in bolus supplements or by continuous infusion (in long-duration interventions).

The dosage of LIMIFEN should be individualized according to age, body weight, physical condition, underlying pathological condition, use of other medications, and type of surgical and anesthetic intervention.

To avoid bradycardia, a small dose of an anticholinergic medication may be administered intravenously (I.V.) just before anesthetic induction.

Dosage for adults:

Use in short procedures and outpatient patients

Small doses of LIMIFEN are more useful in minor and short surgical procedures and in outpatient patients, provided that a cardiopulmonary monitoring equipment is available.

A dose of 7 to 15 micrograms/kg (1 to 2 ml/70 kg) I.V. in bolus is usually sufficient for procedures lasting less than 10 minutes. If the procedure duration exceeds 10 minutes, additional increments of 7 to 15 micrograms/kg (1 to 2 ml/70 kg) every 10 to 15 minutes or as needed should be administered.

Although assisted ventilation should be available, spontaneous breathing should be maintained with a dose of 7 micrograms/kg (1 ml/70 kg) or less, administered slowly; with this technique, increments of 3.5 micrograms/kg (0.5 ml/70 kg) are recommended.

When postoperative nausea occurs, it is usually of short duration and can be controlled with standard measures.

For procedures of medium duration

The initial I.V. dose in bolus should be adjusted according to the expected duration of the surgical procedure as indicated:

When the surgical procedure is more prolonged or aggressive, analgesia can be maintained by:

-either increments of 15 micrograms/kg (2 ml/70 kg) of LIMIFEN as needed (to avoid postoperative respiratory depression, LIMIFEN should not be administered during the last 10 minutes of surgical intervention);

-or a continuous infusion of LIMIFEN at a rate of 1 microgram/kg/min (0.14 ml/70 kg/min) until 5 to 10 minutes before the end of the surgical intervention.

Periods of painful stimuli can be controlled by small additional doses or by increasing the infusion rate.

Lower doses of LIMIFEN may be used when anesthesia is complemented with other agents.

When LIMIFEN is used without N2O/O2or without another inhaled anesthetic, a higher maintenance dose of LIMIFEN is required.

For longer surgical procedures

LIMIFEN can be used as the analgesic component of anesthesia during long-duration surgical procedures, especially when rapid extubation is required. By administering an individually adjusted initial I.V. dose and adjusting the infusion rate according to the severity of the surgical stimulus and the patient's reactions, optimal analgesia and stable autonomic nervous system function can be maintained.

Special populations

Pediatric population

A cardiopulmonary monitoring equipment should be available for use in children of any age, even for short-duration interventions in children with spontaneous breathing.

Data in children, particularly those aged 1 month to 1 year, are limited (see section 5.2).

• Newborns (0 to 27 days):The pharmacokinetics are highly variable in newborns, particularly in premature infants. Clearance and protein binding are lower, and a lower dose of LIMIFEN may be required. Newborns should be closely monitored, and the dose of LIMIFEN should be adjusted according to response.

• Infants and children (28 days to 23 months):Clearance may be higher in infants and children compared to adults. A higher infusion rate of LIMIFEN may be required to maintain analgesia.

• Children (2 to 11 years):Clearance may be slightly higher in children, and a higher infusion rate may be required.

• Adolescents:The pharmacokinetics of alfentanil in adolescents are similar to those in adults, and no specific dosage recommendations are required.

Recommended dosages for pediatric patients

The wide variability in response to LIMIFEN makes it difficult to provide dosage recommendations for younger children. For older children, a bolus dose of 10 to 20 µg/kg of LIMIFEN is considered appropriate for inducing anesthesia (e.g., to supplement propofol or inhalation anesthesia) or as an analgesic. LIMIFEN can be administered in bolus supplements of 5 to 10 µg/kg at appropriate intervals.

For maintaining anesthesia in children during the procedure, LIMIFEN can be administered at an infusion rate of 0.5 to 2 µg/kg/min. The dose should be adjusted according to the needs of each patient. When combined with an intravenous anesthetic, the recommended dose is approximately 1 µg/kg/min.

There may be a higher risk of respiratory complications and muscle rigidity when LIMIFEN is administered to newborns and younger children (see section 4.4 for necessary precautions).

Debilitated and elderly patients

The initial dose should be reduced in elderly patients (over 65 years of age) and in debilitated patients. The effect of the initial dose should be taken into account when determining additional doses.

Administration

LIMIFEN is administered through injection in bolus, or supplements in bolus for increments, or through infusion.

Special warnings and precautions for use

As with all potent opioids, respiratory depression may occur:

Respiratory depression

Respiratory depression is dose-dependent and can be reversed with specific opioid antagonists, but additional doses of these may be required since respiratory depression may last longer than the action of the opioid antagonist. Deep analgesia is accompanied by significant respiratory depression and loss of consciousness that may persist or recur postoperatively. Therefore, patients receiving LIMIFEN should be adequately monitored. Equipment for resuscitation and opioid antagonists should be readily available. Hyperventilation during anesthesia may alter the patient's response to CO2, affecting postoperative breathing.

Risk due to concomitant use with central nervous system depressants, especially benzodiazepines or related medications.

In patients with spontaneous breathing, concomitant use of LIMIFEN and central nervous system depressants, especially benzodiazepines or related medications, may increase the risk of deep sedation, respiratory depression, coma, and death. If LIMIFEN is administered concomitantly with a central nervous system depressant, especially a benzodiazepine or related medication, the effective dose of both medications should be minimized for the shortest duration necessary. Patients should be closely monitored for signs and symptoms of respiratory depression and deep sedation. It is strongly recommended that patients and their caregivers be informed of these symptoms (see Interactions).

Muscle rigidity

It may induce muscle rigidity, which may also include the chest muscles, but this can be prevented by taking the following measures: slow I.V. injection (usually sufficient for low doses), premedication with benzodiazepines, and use of muscle relaxants. Non-epileptic myoclonic movements may occur.

Cardiac disease

If anticholinergic medications are administered in insufficient quantities or if non-vagolytic muscle relaxants are used, bradycardia and even asystole may occur. Bradycardia can be treated with atropine.

Special conditions for dosing

As with other opioids, LIMIFEN may induce hypotension, especially in hypovolemic patients. Appropriate measures should be taken to maintain stable blood pressure.

Alfentanil is metabolized primarily by the cytochrome P450 3A4 enzyme.

Available pharmacokinetic data indicate that alfentanil metabolism may be inhibited by some medications (see Interactions with other medications and other forms of interaction). This may increase the risk of delayed or prolonged respiratory depression, and concomitant use of these medications requires careful patient monitoring, and may require a reduction in the dose of LIMIFEN.

It is recommended to avoid rapid I.V. injections of opioids in patients with compromised intracranial compliance; in these patients, the transient decrease in mean arterial pressure may be accompanied, on occasion, by a brief reduction in cerebral perfusion pressure.

Patients receiving chronic opioid therapy or with a history of opioid dependence may require higher doses.

It is recommended to reduce the dosage in debilitated and elderly patients. As with other opioids, LIMIFEN should be administered with caution in the following states: uncontrolled hypothyroidism, pulmonary diseases, decreased respiratory reserves, alcoholism, and altered hepatic or renal function. These patients require prolonged postoperative monitoring.

Pediatric population

There may be a higher risk of respiratory complications and muscle rigidity when LIMIFEN is administered to newborns and younger children compared to older children and adults. Therefore, pediatric patients of younger age should be monitored immediately after administration of LIMIFEN. A cardiopulmonary monitoring equipment should be available for use in children of any age, even for short-duration interventions in children with spontaneous breathing.

If LIMIFEN is used in newborns and infants, the use of a muscle relaxant should be considered due to the risk of muscle rigidity. All children should be monitored for a sufficient period after the completion of LIMIFEN treatment to ensure return to spontaneous breathing.

In newborns, a lower dose of LIMIFEN may be required due to pharmacokinetic variability.

Newborns should be closely monitored, and the dose of LIMIFEN should be adjusted according to response.

Instructions for correct administration of the preparation

LIMIFEN may be mixed with intravenous infusions of sodium chloride or glucose. Such dilutions are compatible with plastic infusion sets. These should be used within 24 hours after preparation.

Keep this medication out of the reach of children.

Use gloves when opening and/or handling the ampoule.

Exposure to the skin should be treated by rinsing the affected area with water. Avoid the use of soap, alcohol, and other cleaning materials that may cause chemical or physical abrasions to the skin.

1. Hold the ampoule between the index and middle fingers, leaving the tip of the ampoule free.
2. With the other hand, hold the tip of the ampoule with the index finger against the neck of the ampoule and the middle finger at the colored point in parallel with the colored rings of identification.
3. While holding the finger in that position, break the tip of the ampoule while firmly holding the other part of the ampoule in the hand.