Fendivia^® (Transdermal system) Instructions for Use

Marketing Authorization Holder

Takeda Pharma A/S (Denmark)

Manufactured By

LTS Lohmann Therapie-Systeme, AG (Germany)

ATC Code

N02AB03 (Fentanyl)

Active Substance

Fentanyl (Rec.INN registered by WHO)

Dosage Forms

	Fendivia®	Transdermal therapeutic system (TTS) 12.5 mcg/h: 5 pcs.
		Transdermal therapeutic system (TTS) 25 mcg/h: 5 pcs.
		Transdermal therapeutic system (TTS) 50 mcg/h: 5 pcs.
		Transdermal therapeutic system (TTS) 75 mcg/h: 5 pcs.
		Transdermal therapeutic system (TTS) 100 mcg/h: 5 pcs.

Dosage Form, Packaging, and Composition

Transdermal therapeutic system (TTS) with a fentanyl release rate of 12.5 mcg/h (approximately 0.3 mg/day) and a contact surface area of 4.2 cm²; it is a semi-transparent patch (width 18±0.5 mm, length 24±0.5 mm) of rectangular shape with rounded corners on a removable transparent protective liner; the protective liner is larger than the patch and is divided by a sinusoidal cut into two parts; the patch has a brown inscription “Fentanyl 12.5 μg/hour” applied by color printing.

Composition of the outer protective film polyethylene terephthalate film.
Composition of the reservoir layer silicone adhesive layer, dimethicone (E900).
Composition of the microreservoirs containing Fentanyl dipropylene glycol, hypromellose (E463).
Composition of the release membrane ethylene and vinyl acetate copolymer.
Composition of the skin-adhesive layer silicone adhesive layer, dimethicone (E900).
Composition of the removable protective liner polyester film with a fluorine-containing polymer coating.

1 pc. – thermowelded bags (5) – cardboard packs.

Transdermal therapeutic system (TTS) with a fentanyl release rate of 25 mcg/h (approximately 0.6 mg/day) and a contact surface area of 8.4 cm²; it is a semi-transparent patch (width 24.6±0.5 mm, length 37±0.5 mm) of rectangular shape with rounded corners on a removable transparent protective liner; the protective liner is larger than the patch and is divided by a sinusoidal cut into two parts; the patch has a red inscription “Fentanyl 25 μg/hour” applied by color printing.

Composition of the outer protective film polyethylene terephthalate film.
Composition of the reservoir layer silicone adhesive layer, dimethicone (E900).
Composition of the microreservoirs containing Fentanyl dipropylene glycol, hypromellose (E463).
Composition of the release membrane ethylene and vinyl acetate copolymer.
Composition of the skin-adhesive layer silicone adhesive layer, dimethicone (E900).
Composition of the removable protective liner polyester film with a fluorine-containing polymer coating.

1 pc. – thermowelded bags (5) – cardboard packs.

Transdermal therapeutic system (TTS) with a fentanyl release rate of 50 mcg/h (approximately 1.2 mg/day) and a contact surface area of 16.8 cm²; it is a semi-transparent patch (width 34±0.5 mm, length 51.3±0.5 mm) of rectangular shape with rounded corners on a removable transparent protective liner; the protective liner is larger than the patch and is divided by a sinusoidal cut into two parts; the patch has a green inscription “Fentanyl 50 μg/hour” applied by color printing.

Composition of the outer protective film polyethylene terephthalate film.
Composition of the reservoir layer silicone adhesive layer, dimethicone (E900).
Composition of the microreservoirs containing Fentanyl dipropylene glycol, hypromellose (E463).
Composition of the release membrane ethylene and vinyl acetate copolymer.
Composition of the skin-adhesive layer silicone adhesive layer, dimethicone (E900).
Composition of the removable protective liner polyester film with a fluorine-containing polymer coating.

1 pc. – thermowelded bags (5) – cardboard packs.

Transdermal therapeutic system (TTS) with a fentanyl release rate of 75 mcg/h (approximately 1.8 mg/day) and a contact surface area of 25.2 cm²; it is a semi-transparent patch (width 42±0.5 mm, length 61.7±0.5 mm) of rectangular shape with rounded corners on a removable transparent protective liner; the protective liner is larger than the patch and is divided by a sinusoidal cut into two parts; the patch has a light blue inscription “Fentanyl 75 μg/hour” applied by color printing.

Composition of the outer protective film polyethylene terephthalate film.
Composition of the reservoir layer silicone adhesive layer, dimethicone (E900).
Composition of the microreservoirs containing Fentanyl dipropylene glycol, hypromellose (E463).
Composition of the release membrane ethylene and vinyl acetate copolymer.
Composition of the skin-adhesive layer silicone adhesive layer, dimethicone (E900).
Composition of the removable protective liner polyester film with a fluorine-containing polymer coating.

1 pc. – thermowelded bags (5) – cardboard packs.

Transdermal therapeutic system (TTS) with a fentanyl release rate of 100 mcg/h (approximately 2.4 mg/day) and a contact surface area of 33.6 cm²; it is a semi-transparent patch (width 49±0.5 mm, length 70±0.5 mm) of rectangular shape with rounded corners on a removable transparent protective liner; the protective liner is larger than the patch and is divided by a sinusoidal cut into two parts; the patch has a gray inscription “Fentanyl 100 μg/hour” applied by color printing.

Composition of the outer protective film polyethylene terephthalate film.
Composition of the reservoir layer silicone adhesive layer, dimethicone (E900).
Composition of the microreservoirs containing Fentanyl dipropylene glycol, hypromellose (E463).
Composition of the release membrane ethylene and vinyl acetate copolymer.
Composition of the skin-adhesive layer silicone adhesive layer, dimethicone (E900).
Composition of the removable protective liner polyester film with a fluorine-containing polymer coating.

1 pc. – thermowelded bags (5) – cardboard packs.

Clinical-Pharmacological Group

Pure opioid receptor agonist. Analgesic

Pharmacotherapeutic Group

Narcotic analgesic agent

Pharmacological Action

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

It activates the endogenous antinociceptive system and thus disrupts interneuronal transmission of pain impulses at various levels of the CNS, and also changes the emotional perception of pain. In its pharmacological properties, Fentanyl is similar to morphine: it increases the pain threshold in response 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 potency (it is 100 times more potent than morphine in analgesic effect), shorter duration of action, and more pronounced ability to depress the respiratory center.

When administered intravenously, the maximum effect develops within 1-3 minutes and lasts for 15-20 minutes; when administered intramuscularly, 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. It is metabolized in the liver (with the participation of the isoenzyme CYP3A4, N-dealkylation and hydroxylation), kidneys, intestines, and adrenal glands. All metabolites are inactive. It is 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; 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

Apply the transdermal system to intact, non-irritated, non-irradiated, flat skin on the upper torso or arm. Remove the protective liner and press the patch firmly in place with the palm of the hand for at least 30 seconds.

Ensure the patch adheres completely, especially around the edges. Do not apply to areas with excessive hair; clip hair if necessary. Do not shave the application site. Do not use soaps, oils, or lotions on the skin prior to application as this may impair adhesion.

The initial dose must be individualized based on the patient’s prior opioid exposure. For opioid-naïve patients, initiate therapy with the lowest available strength (12.5 mcg/h). For patients switching from other opioids, calculate the equivalent 24-hour fentanyl dose using specific conversion guidelines.

Change the patch every 72 hours. Rotate the application site; do not apply a new patch to the same skin area for at least several days. Monitor patients closely for respiratory depression for the first 24-72 hours after initiation and following any dose increase.

Disposal of used or unused patches must be performed with care. Fold the used patch so the adhesive side adheres to itself and flush it down the toilet immediately. Do not place in household trash where it could be found by children or pets.

To discontinue therapy, gradually reduce the dose to prevent withdrawal symptoms. Do not abruptly stop treatment. The remaining fentanyl in the system continues to be absorbed for 24 hours or more after patch removal.

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 failure, respiratory failure (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; cesarean section and other obstetric operations at the stage before fetal extraction (risk of respiratory depression in the newborn); severe 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 failure, pregnancy, simultaneous use of insulin, corticosteroids and antihypertensive drugs, traumatic brain injury, prostatic hyperplasia, urethral strictures, suicidal tendencies, hyperthermia, use of MAO inhibitors, elderly patients, debilitated patients.

Use in Pregnancy and Lactation

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

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

It is not recommended for use during labor and delivery (including cesarean 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 sedation 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 the recommended doses and dosage forms intended for this age category. It is necessary to strictly follow the instructions in the prescribing information for fentanyl preparations regarding contraindications for the use of specific dosage forms of fentanyl in children of different ages.

Geriatric Use

Special caution is required when used in elderly patients due to the high risk of adverse 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, sudden 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 its duration of action is possible.

The physician should consider the possibility of fentanyl abuse.

Effect on the ability to drive vehicles and operate machinery

Patients should avoid driving vehicles 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 adverse effects.

It enhances the effect of antihypertensive drugs. Beta-blockers may 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-cholinolytic 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-cholinolytic 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 cardiovascular adverse effects.

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

Tricyclic antidepressants also increase the risk of respiratory center depression.

Nitrous oxide increases muscle rigidity.

Fentanyl should not be combined with narcotic analgesics from the group of partial agonists (buprenorphine) and opioid receptor agonist-antagonists (nalbuphine, butorphanol, tramadol) due to the risk of reduced 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 15°C (59°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.