Label: Patient Information

Fentanest 0.05 mg/ml Injectable Solution

Fentanyl Citrate

Fentanest contains fentanyl as its active ingredient. It is a potent pain relief medication, belonging to the group of narcotic analgesics or opioids.

Fentanest is used:

• For general or local anesthesia, as a complementary narcotic analgesic.
• As pre-anesthetic analgesic medication to help induce and maintain general and local anesthesia, when administered with a neuroléptic medication (a medication that produces sedation of the nervous system), such as droperidol.
• As an anesthetic with oxygen, in high-risk patients undergoing surgical interventions.

No use Fentanest

• If you are allergic to fentanyl or any of the other components of this medication (listed in section 6).
• If you have a known intolerance to this medication or other morphine-like medications (medications that have a similar effect to morphine).
• If you have a head trauma, increased intracranial pressure, or coma.
• If the patient is under 2 years old.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to use Fentanest if:

You or a family member has ever abused or been dependent on alcohol, prescription medications, or illegal drugs (“addiction”).

- You are a smoker.

- You have ever had mood problems (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for another mental illness.

As with other potent opioids, respiratory depression (slow or weak breathing that cannot provide adequate ventilation and perfusion to the lungs) depends on the dose and can be reversed with the use of a narcotic antagonist (such as naloxone). However, it may be necessary to administer additional doses of this antagonist, as respiratory depression can last longer than the action of the opioid antagonist. Deep analgesia is accompanied by marked respiratory depression that can persist or recur during the postoperative period. For this reason, patients must remain under adequate surveillance. A resuscitation team and opioid antagonists must be available. Hyperventilation (faster and deeper breathing than normal) during anesthesia can alter the patient's response to carbon dioxide, affecting breathing in the postoperative period.

It may cause muscle rigidity, including chest muscle rigidity, which can be prevented by taking the following measures: very slow intravenous injection (which is usually sufficient for low doses), premedication with benzodiazepines, and administration of muscle relaxants.

It may cause non-epileptic myoclonic movements (sudden, involuntary movements).

If the patient does not receive sufficient amounts of an anticholinergic medication (medications that calm intestinal muscle spasms), or when fentanyl is associated with a non-vagolytic muscle relaxant, it may cause bradycardia (decrease in heart rate), and even cardiac arrest.

Bradycardia can be treated with the administration of atropine.

Opioids can induce low blood pressure, especially in patients with a significant decrease in the normal amount of blood (hypovolemia). Appropriate measures should be taken to maintain stable blood pressure.

It should be avoided to use rapid bolus injection of opioids in patients with compromised cerebral function; transient decrease in mean blood pressure has sometimes been accompanied by transient reduction in cerebral perfusion in these patients.

If treatment is interrupted, withdrawal symptoms may appear. Inform your doctor or nurse if you think you are experiencing this (see also section 4. Possible side effects).

Dependence and Addiction

The repeated use of opioid analgesics can make the medication less effective (the person taking it becomes accustomed to it). It can also produce dependence and addiction, which can lead to potentially fatal overdose. It is essential to consult your doctor if you are concerned about becoming dependent on Fentanest.

Especially, inform your doctor or pharmacist if you are taking:

• Some analgesics for neuropathic pain (gabapentin and pregabalin).

Patients under prolonged treatment with opioids or with a history of opioid dependence may require higher doses.

It is recommended to reduce the dose in elderly and debilitated patients. A careful adjustment of the dose of this medication is necessary in patients with the following disorders: hypothyroidism (decrease in thyroid hormone levels), pulmonary disease, respiratory depression, alcoholism, renal or hepatic dysfunction. These patients require additional prolonged postoperative monitoring.

In the simultaneous use of fentanyl and droperidol, the doctor must know the characteristics of each medication, especially the differences in the duration of action. The administration of these medications at the same time increases the possibility of low blood pressure. Droperidol can cause uncontrolled body or facial movements, which can be controlled with medications for Parkinson's disease.

Use of Fentanest with Other Medications

Inform your doctor or pharmacist that you are using or have recently used or may need to use any other medication.

It should be avoided to use simultaneously the derivatives of barbituric acid with fentanyl, as they can increase the depressive effect of fentanyl on breathing.

It is not recommended to use fentanyl simultaneously with buprenorphine, nalbuphine, or pentazocine (medications indicated for pain relief), as they can cause withdrawal symptoms in opioid-dependent patients.

The simultaneous use of Fentanest with medications to slow down the activity of the central nervous system (other central nervous system depressants) can produce additive depressive effects, hypoventilation, and hypotension, and deep sedation or coma. Central nervous system depressants include:

• Opioids,
• Antipsychotics,
• Hypnotics,
• General anesthetics,
• Muscle relaxants,
• Sedating antihistamines,
• Alcoholic beverages.

Epinephrine should never be used as a vasoactive agent with fentanyl, as it can cause hypotension.

Therefore, the simultaneous use of any of the mentioned drugs and substances requires patient surveillance.

It has been reported that monoamine oxidase inhibitors (a certain group of antidepressant medications), produce an increase in the effect of narcotic analgesics, especially in patients with heart failure. Therefore, fentanyl should not be used during the 14 days following the interruption of treatment with this type of medication. Generally, it is recommended to suspend the administration of monoamine oxidase inhibitors in the two weeks prior to any surgical intervention. However, several reports describe the use of fentanyl during surgical interventions in patients receiving monoamine oxidase inhibitors without any interactions occurring.

The simultaneous use of potent CYP3A4 inhibitors, e.g.: ritonavir, ketoconazole, itraconazole, macrolide antibiotics, with fentanyl could lead to an increase in plasma concentrations of fentanyl, which could increase or prolong both therapeutic and adverse effects and could cause severe respiratory depression. In this situation, special care and observation of the patient are appropriate. The simultaneous use of ritonavir or other potent CYP3A4 inhibitors with fentanyl is not recommended, unless the patient is constantly monitored.

The concomitant use of fentanyl and sedatives such as benzodiazepines or related medications increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes fentanyl along with sedatives, the dose and duration of concomitant treatment should be limited by your doctor.

Inform your doctor about all sedatives you are taking and follow your doctor's recommendations carefully regarding the dose. It may be helpful to inform friends or family members to be aware of the mentioned signs and symptoms. Contact your doctor when you experience such symptoms.

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

The safety of fentanyl use during pregnancy has not been established. Fentanyl should not be used during pregnancy, unless it is clearly necessary. Prolonged use during pregnancy can cause withdrawal symptoms in the newborn.

Fentanyl should not be used during childbirth (including cesarean section) as fentanyl crosses the placenta and can cause respiratory depression in the newborn.

Fentanyl passes into breast milk and can cause sedation and respiratory depression in the newborn. Therefore, breastfeeding is not recommended for 24 hours after medication administration.

Driving and Operating Machines

Do not drive or operate tools or machines after receiving Fentanest, as this medication can affect your reaction time. Your doctor will indicate how long you should wait before driving or operating machines.

Warnings about Doping

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

Fentanest contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per 2, 3, and 5 ml ampoule; this is, essentially “sodium-free”.

This medication contains 35.4 mg of sodium (main component of table salt/for cooking) in each 10 ml ampoule. This is equivalent to 1.81% of the recommended daily maximum sodium intake for an adult.

Dosage

This medication should be administered by a doctor or nurse. Your doctor will determine the most suitable dose for you based on your age, weight, overall health, type of procedure, and use of other medications.

Geriatric and Debilitated Patients

The dose administered to elderly patients (65 years or older) or debilitated patients just before surgery is less than that indicated for other adults. If the doctor considers it necessary, an additional dose may be administered later.

Children 2 Years of Age and Older

The dose administered to children just before surgery depends on the child's weight. If the doctor considers it necessary, an additional dose may be administered later.

Adolescents aged 12 to 17 years receive the same dose as adults.

Children Under 2 Years of Age

There is no experience with the use of this medication in children under 2 years of age. Therefore, it is not recommended to administer this medication in this age range.

Patients with Renal Problems

The doctor may decide to reduce the dose administered to patients with renal problems.

Obese Patients

The dose administered to obese patients just before surgery may be lower than that indicated for other adults. If the doctor considers it necessary, an additional dose may be administered later.

Route of Administration

This medication can be administered through a vein or muscle.

If You Are Given More Fentanil Than You Should

Since this medication will be administered in the hospital and by a doctor, it is unlikely that you will be given too much. However, consult your doctor or nurse if you think you have been given too much medication or if you experience respiratory difficulties, dizziness, or symptoms of low blood pressure or muscle rigidity.A overdose can also cause a brain disorder (known as toxic leukoencephalopathy).

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medications, this medication may cause side effects, although not everyone will experience them.

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

• Drowsiness.
• Headache, dizziness.
• Nausea, vomiting, constipation.
• Sweating, pruritus.

Common(may affect up to 1 in 10 people):

• Sedation, nervousness, loss of appetite, depression.
• Xerostomia (dry mouth), upper abdominal discomfort (dyspepsia).
• Skin reactions at the application site.

Uncommon(may affect up to 1 in 100 people):

• Euphoria, amnesia, insomnia, hallucinations, agitation.
• Tremor, paresthesia (tingling sensation), speech disorders, muscle rigidity, myoclonus (involuntary, rapid, and irregular muscle movements).
• Tachycardia, bradycardia.
• Hypertension, hypotension.
• Dyspnea (shortness of breath), hypoventilation.
• Diarrhea.
• Acute skin eruptions (exanthema), skin redness (erythema).
• Urinary retention.
• Dysphagia (difficulty swallowing).

Rare(may affect up to 1 in 1,000 people):

• Arrhythmia.
• vasodilation.
• Hiccup.
• Edema (swelling), feeling of cold.

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

• Severe allergic reaction throughout the body (anaphylactic reaction).
• Delirium, states of excitement, asthenia, anxiety, confusion, sexual dysfunction, withdrawal syndrome symptoms.
• Ataxia (clumsiness or loss of coordination), seizures (including clonic seizures and grand mal seizures).
• Decreased vision in one or both eyes (amblyopia)
• Respiratory depression, apnea.
• Flatulence with pain, intestinal obstruction.
• Cystitis (painful urination), decreased urine production (oliguria).

Frequency not known(cannot be estimated from available data):

• Development of physical and psychological dependence and tolerance with prolonged use of fentanyl.
• Delirium (symptoms may include agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not there, sleep disorders, nightmares).
• Withdrawal syndrome symptoms (may manifest as the appearance of the following adverse effects: nausea, vomiting, diarrhea, anxiety, chills, tremor, and sweating).

Respiratory depression is the most severe effect of fentanyl.

Other adverse effects:

Laryngospasm.

After administration of fentany with another neuroleptic, such as droperidol, the following adverse reactions may occur: tremor, nervousness, postoperative hallucinations, and extrapyramidal symptoms.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es/. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

No special storage conditions are required. Store in the original packaging to protect it from light. Use immediately after opening.

Do not use this medication after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations. By doing so, you will help protect the environment.

Composition of Fentanest

• The active principle is fentanyl. Each ml of solution contains 0.0785 mg of fentanyl citrate, equivalent to 0.05 mg of fentanyl.

Each 2 ml ampoule contains 0.157 mg of fentanyl citrate, equivalent to 0.1 mg of fentanyl.

Each 3 ml ampoule contains 0.2355 mg of fentanyl citrate, equivalent to 0.15 mg of fentanyl.

Each 5 ml ampoule contains 0.3925 mg of fentanyl citrate, equivalent to 0.25 mg of fentanyl.

Each 10 ml ampoule contains 0.785 mg of fentanyl citrate, equivalent to 0.5 mg of fentanyl.

• The other components are sodium chloride and water for injection.

Appearance of the product and contents of the package

Boxes of 10 ampoules of 2 ml, 5 ampoules of 3 ml, 10 ampoules of 3 ml, 10 ampoules of 5 ml or 10 ampoules of 10 ml.

Only some package sizes may be marketed.

The ampoules are transparent and contain a transparent and colourless liquid.

Holder of the marketing authorization and responsible for manufacturing

Kern Pharma, S.L.

Venus, 72 - Pol. Ind.Colón II

08228 Terrassa - Barcelona

Spain

Last review date of this leaflet: March 2025

The detailed and updated information on this medicine is available on 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:

Consult the Summary of Product Characteristics or the Product Information for a complete description and other information.

Dosage and administration

This medicine should only be administered in an environment where it is possible to control the respiratory tract and by professionals who can monitor the respiratory tract (see the Summary of Product Characteristics section 4.4).

The dose of this medicine should be determined individually according to age, body weight, physical condition, underlying pathological condition, use of other medications and type of surgical and anaesthetic intervention.

Adults

Premedication

As premedication (30-60 minutes before surgery) the usual dose is 0.7 to 1.4?g/kg (0.014 to 0.028 mL/kg) of Fentanest by intramuscular or slow intravenous injection.

Use as an analgesic supplement to local anaesthesia

Fentanest injectable can be administered as an analgesic supplement to local anaesthesia in doses of 0.35 to 1.4?g/kg (0.007 to 0.028 mL/kg) by intramuscular or intravenous injection.

Use as an analgesic supplement to general anaesthesia.

Low doses: 2 µg/kg (0.04 mL/kg)

Fentanyl at low doses is very useful in minor but painful surgical interventions.

Moderate doses: 2 – 20 µg/kg (0.04-0.4 mL/kg)

When the surgical procedure is more complicated, a moderate dose is required.

The duration of action is dose-dependent.

High doses: 20 – 50 µg /kg (0.4-1 mL/kg)

During major surgical interventions where the procedure is more prolonged, the administration of 20 – 50µg/kg (0.4-1 mL/kg) of fentanyl with nitrous oxide/oxygen has shown a dampening effect.

Your doctor will perform postoperative ventilation and observation.

Increases of 25- 250 micrograms/kg (0.5 – 5 ml) may be administered as needed and according to the duration of the surgical intervention.

Use as an anaesthetic agent.

When it is particularly important to reduce the surgical stimulus reaction, doses of 50 – 100?g/kg (1-2 mL/kg) may be administered by intramuscular or intravenous injection with oxygen and a muscle relaxant. This technique provides anaesthesia without the additional use of anaesthetic agents.

In some cases, it may be necessary to administer doses up to 150?g/kg (3 mL/kg) to achieve an anaesthetic effect.

Fentanyl has been used in open-heart surgery and certain major surgical interventions in patients for whom heart protection against excessive oxygen is particularly indicated.

Use in elderly and debilitated patients

As with other opioids, the dose administered in elderly or debilitated patients should be reduced.

Use in children

For induction and maintenance of anaesthesia in children aged 2 to 12 years, it is recommended to reduce the dose to 2 – 3?g/kg (0.04-0.06 mL/kg).

Use in patients with renal insufficiency

Data from a study in which fentanyl was administered intravenously to patients undergoing renal transplantation suggest that fentanyl elimination may be reduced in this population. If patients with renal impairment receive fentanyl, they should be closely monitored for signs of fentanyl toxicity and the dose reduced as necessary (see Dosage and Administration).

Obese patients

In obese patients, there is a risk of overdose if the dose is calculated based on body weight. The dose for obese patients should be calculated based on lean body mass rather than just body weight.

Warnings and precautions for special use

As with other strong opioids:

Respiratory depression is dose-related and can be reversed with the administration of a narcotic antagonist (naloxone), but additional doses of this antagonist may be necessary since respiratory depression may have a longer duration of action than opioid antagonists. Deep analgesia is accompanied by marked respiratory depression that may persist or recur in the postoperative period. Therefore, patients should be closely monitored. It is necessary to have resuscitation equipment and narcotic antagonists available.

Hyperventilation during anaesthesia may modify the patient's response to CO2, affecting respiration in the postoperative period.

Rigidity of the muscles, including thoracic muscles, may occur, which can be prevented by taking the following measures: slow intravenous injection (which is usually sufficient for low doses), premedication with a benzodiazepine and administration of muscle relaxants.

Myo-clonic movements may occur.

Bradycardia and possibly asystole may occur if the patient receives an insufficient amount of anticholinergic or if Fentanest is combined with a non-vagolytic muscle relaxant. Bradycardia can be treated with atropine.

Opioids can cause hypotension, especially in patients with hypovolemia. Appropriate measures should be taken to maintain stable blood pressure.

It should be avoided to inject opioids rapidly in bolus in patients with altered cerebrovascular distensibility, as a transient reduction in mean arterial pressure has been accompanied by a transient reduction in cerebral blood flow in these patients.

Patients who receive prolonged treatment with opioids or have a history of opioid abuse may require higher doses.

If Fentanest is administered with droperidol, the doctor should be aware of the properties of each medication, especially the difference in duration of action. The incidence of hypotension increases when this combination is administered. Droperidol may cause extrapyramidal symptoms that can be controlled with antiparkinsonian drugs

Pharmacological dependence and potential for abuse

Tolerance, physical and psychological dependence may develop after repeated administration of opioids. The risks increase in patients with a personal history of substance abuse (including drug or alcohol abuse).

Abstinence syndrome

Repeated administration at short intervals for prolonged periods may lead to the development of an abstinence syndrome after treatment interruption, which may manifest as the appearance of the following adverse effects: nausea, vomiting, diarrhoea, anxiety, shivering, tremors and sweating.

Instructions for opening the ampoules

1. Hold the ampoule between the index and middle fingers with the tip of the ampoule pointing upwards.

2. Hold the tip of the ampoule with the index finger of the other hand against the neck of the ampoule. Place the middle finger to cover the tip of the ampoule, as shown in the diagram.

3. With the index fingers together, press the tip to open the ampoule.

Incompatibilities

In the absence of compatibility studies, this medicine should not be mixed with others.

Contraindications

• Hypersensitivity to the active principle or to any of the excipients included in the Summary of Product Characteristics, or to other opioids.
• Respiratory insufficiency without mechanical ventilation, due to the specific respiratory depressive effect of morphine-like drugs.