Fentanyl (Solution, Transdermal system) Instructions for Use

ATC Code

N01AH01 (Fentanyl)

Active Substance

Fentanyl (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Pure opioid receptor agonist. Analgesic

Pharmacotherapeutic Group

Anesthetics; preparations for general anesthesia; opioid analgesics

Pharmacological Action

Opioid analgesic. Agonist of opioid receptors, interacts predominantly with μ-receptors.

It activates the endogenous antinociceptive system and thus disrupts interneural transmission of pain impulses at various levels of the CNS, and also changes the emotional coloring of pain. In terms of pharmacological properties, Fentanyl is similar to morphine: it increases the pain sensitivity threshold to pain stimuli of various modalities, inhibits conditioned reflexes, has a depressant effect on the CNS, and suppresses the activity of the respiratory center. It differs from morphine in its greater activity (it is 100 times more potent than morphine in analgesic effect), shorter duration of action, and more pronounced ability to depress the respiratory center.

With intravenous administration, the maximum effect develops within 1-3 minutes and lasts for 15-20 minutes; with intramuscular administration, the maximum effect develops within 3-10 minutes, and the duration of action is 1-2 hours.

Pharmacokinetics

To achieve an average level of analgesia, the plasma concentration of fentanyl should be 15-20 ng/ml. Plasma protein binding is 79-87%. Clearance is 400-500 ml/min, T_1/2 is 10-30 minutes, V_d is 60-80 L. It is rapidly redistributed from the blood and brain into muscles and adipose tissue. It is excreted in breast milk. Metabolized in the liver (with the participation of the isoenzyme CYP3A4, N-dealkylation and hydroxylation), kidneys, intestines, and adrenal glands. All metabolites are inactive. Excreted by the kidneys (75% as metabolites and 10% unchanged) and with bile (9% as metabolites).

Indications

For parenteral administration

Pain syndrome of severe and moderate intensity: postoperative pain, angina pectoris, myocardial infarction, pain in cancer patients. Premedication before surgical operations. As an additional analgesic for operations under local anesthesia. Postoperative anesthesia. Neuroleptanalgesia (in combination with droperidol).

For transdermal administration

Chronic pain in cancer diseases; intractable pain; chronic pain syndrome in children over 2 years of age who have been taking opioid analgesics.

For intranasal administration

For intranasal administration: for the relief of breakthrough pain in adults who are already receiving opioid analgesics for chronic pain due to cancer.

ICD codes

Dosage Regimen

Select the dosage regimen individually based on the patient’s age, body weight, clinical status, nature of pain, and concomitant therapy.

For transdermal systems, apply to intact, non-irritated, non-hairy skin on a flat surface of the torso or upper arm. Use a different application site for each new system. Do not expose the application site to direct heat sources.

Initiate transdermal therapy at the lowest possible dose. For opioid-naïve patients, do not initiate with transdermal fentanyl. Convert patients from other opioids to fentanyl transdermal system using official equianalgesic conversion tables and reduce the calculated dose by 25-50% due to incomplete cross-tolerance.

Monitor patients closely for respiratory depression for 24-72 hours after initial application and following any dose increase. The analgesic effect develops gradually; provide supplemental short-acting analgesia for breakthrough pain during this period.

Change transdermal systems every 72 hours. Adjust the dose based on the average use of supplemental analgesia and the presence of adverse effects. Do not increase the dose more frequently than every 6 days for the 72-hour system.

For intravenous administration, titrate to effect. Administer slowly over 1-3 minutes. For anesthesia, a typical IV induction dose is 2-50 mcg/kg. For postoperative pain, use doses of 50-100 mcg IM or IV, repeated every 1-2 hours as needed.

For intranasal administration, use only for breakthrough cancer pain in opioid-tolerant adults. The initial dose is a single 100 mcg spray into one nostril. If adequate analgesia is not achieved, titrate subsequent doses.

Reduce the dose in elderly, cachectic, or debilitated patients and in those with renal or hepatic impairment. Closely monitor for signs of CNS and respiratory depression.

When discontinuing transdermal therapy, gradually taper the dose to prevent withdrawal symptoms. Do not abruptly stop treatment.

Adverse Reactions

From the respiratory system bronchospasm, laryngospasm, respiratory depression up to arrest (high doses).

From the nervous system headache, depression or paradoxical excitation of the CNS, convulsions, increased intracranial pressure.

From the sensory organs blurred vision, diplopia.

From the digestive system nausea, vomiting, constipation, hepatic colic (in patients with a history of it), flatulence, spasm of the sphincter of Oddi.

Other: allergic reactions of varying severity, bradycardia (up to cardiac arrest), decreased blood pressure, urinary retention, short-term muscle rigidity (including chest muscles), increased sweating, drug dependence, tolerance, withdrawal syndrome.

Local reactions with cutaneous application, skin rash, erythema, itching are possible.

Contraindications

Hypersensitivity to fentanyl; impaired consciousness, brain tumors; bradyarrhythmia, arterial hypotension, hepatic and/or renal insufficiency, respiratory insufficiency (pneumonia, atelectasis and pulmonary infarction, bronchial asthma, tendency to bronchospasm); intracranial hypertension. Severe depression of the respiratory center, acute surgical diseases of the abdominal organs before diagnosis; caesarean section and other obstetric operations in the stage before fetal extraction (risk of respiratory depression in the newborn); pronounced pulmonary hypertension, extrapyramidal disorders; for parenteral administration – children under 1 year of age; for intranasal administration – therapy for acute pain other than breakthrough, previous radiotherapy of the facial area, recurrent nosebleeds; children under 18 years of age; for cutaneous application – irritated, irradiated skin at the application site, children under 2 years of age.

With caution

Myasthenia gravis, hypothyroidism, lung diseases, respiratory failure, alcoholism, renal/hepatic insufficiency, pregnancy, simultaneous use of insulin, corticosteroids and antihypertensive drugs, traumatic brain injury, prostatic hyperplasia, urethral strictures, suicidal tendency, hyperthermia, use of MAO inhibitors, elderly patients, debilitated patients.

Use in Pregnancy and Lactation

Use during pregnancy is only possible if the intended benefit to the mother outweighs the potential risk to the fetus.

Long-term therapy with fentanyl during pregnancy can lead to the development of withdrawal syndrome in the newborn.

It is not recommended for use during labor and delivery (including caesarean section), because Fentanyl crosses the placental barrier and can cause respiratory depression in the fetus. If Fentanyl is still used, an antidote for the child must be prepared.

Fentanyl is excreted in breast milk and can cause sedative effects and respiratory depression in the newborn. Fentanyl should not be used during breastfeeding. Breastfeeding should not be started earlier than 5 days after the last administration of fentanyl.

During the use of fentanyl, women of childbearing age should use reliable methods of contraception.

Use in Hepatic Impairment

Use with caution in cases of impaired liver function.

Use in Renal Impairment

Use with caution in cases of impaired renal function.

Pediatric Use

It can be used in children of the appropriate age categories strictly according to the indications, in recommended doses and dosage forms intended for this age category. It is necessary to strictly follow the instructions in the fentanyl drug leaflets regarding contraindications for the use of specific fentanyl dosage forms in children of different ages.

Geriatric Use

Special caution is required when using in elderly patients due to the high risk of developing side effects.

Special Precautions

The use of fentanyl is recommended in the presence of an anesthesiologist and under conditions of resuscitation readiness.

In the postoperative period, the patient must be under careful observation.

With intravenous administration at a dose of 100-500 mcg, sharp respiratory depression up to apnea is possible.

In patients with reduced body weight, during prolonged operations, or in case of frequent repeated use of fentanyl, an increase in the duration of its action is possible.

The physician should consider the possibility of fentanyl abuse.

Effect on the ability to drive vehicles and mechanisms

Patients should avoid driving and other activities requiring high concentration and speed of psychomotor reactions for 24 hours after fentanyl administration.

Drug Interactions

Ethanol and antihistamines with sedative effects increase the likelihood of side effects.

It enhances the effect of antihypertensive drugs. Beta-blockers can reduce the frequency and severity of the hypertensive reaction in cardiac surgery (including during sternotomy) but increase the risk of bradycardia.

Benzodiazepines prolong recovery from neuroleptanalgesia.

MAO inhibitors increase the risk of severe complications.

Muscle relaxants prevent or eliminate muscle rigidity; muscle relaxants with m-cholinoblocking activity (including pancuronium bromide) reduce the risk of bradycardia and hypotension (especially against the background of beta-blockers and other vasodilators) and may increase the risk of tachycardia and hypertension; muscle relaxants without m-cholinoblocking activity (including suxamethonium) do not reduce the risk of bradycardia and arterial hypotension (especially against the background of a burdened cardiac history) and increase the risk of severe side effects from the cardiovascular system.

Fentanyl should be used with caution against the background of general anesthetics, hypnotics, and neuroleptics to avoid excessive CNS depression and suppression of the respiratory center activity.

Tricyclic antidepressants also increase the risk of respiratory center suppression.

Nitrous oxide enhances muscle rigidity.

Fentanyl should not be combined with narcotic analgesics from the group of partial agonists (buprenorphine) and agonist-antagonists of opioid receptors (nalbuphine, butorphanol, tramadol) due to the risk of weakening analgesia.

When conducting concomitant treatment with insulin preparations, antihypertensive agents, and corticosteroids, Fentanyl should be used in reduced doses.

The analgesic effect and side effects of opioid agonists (morphine, trimeperidine) in the therapeutic dose range are additive to the effects of fentanyl.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.