Active ingredients: Fentanyl
Durogesic 12 micrograms / hour transdermal patch
Durogesic 25 micrograms / hour transdermal patch
Durogesic 50 micrograms / hour transdermal patch
Durogesic 75 micrograms / hour transdermal patch
Durogesic 100 micrograms / hour transdermal patch
Indications Why is Durogesic used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
The active component of Durogesic is fentanyl, a potent pain reliever belonging to the class of narcotic analgesics.
THERAPEUTIC INDICATIONS
Adults:
Durogesic is indicated in the treatment of chronic pain (such as cancer pain) and rebellious pain that requires opiate-based "analgesia."
Children:
Durogesic is indicated for the long-term treatment of severe pain in children 2 years of age and older who are already being treated with opioids.
Contraindications When Durogesic should not be used
Durogesic is contraindicated in patients with known hypersensitivity to fentanyl or to any of the excipients present in the patch.
Durogesic is generally contraindicated in pregnancy.
Durogesic is contraindicated during breastfeeding
Durogesic is contraindicated for the treatment of acute or postoperative pain, as titration is not possible during short-term use.
Durogesic is contraindicated in severe respiratory depression.
Precautions for use What you need to know before taking Durogesic
Durogesic is a medicinal product that can be life-threatening for children. This also applies to used transdermal patches. Please note that the shape and color of this medicinal product can be attractive to a child and this in some cases can lead to a fatal outcome. Durogesic can have life-threatening side effects in people who are not routinely using prescribed opioid medicines.
Durogesic should be used with particular caution in elderly patients and in patients with chronic lung disease, brain, heart, liver, kidney disease or in case of severe constipation.
Warn the doctor of the possible presence of such pathologies.
Opioid-naïve patients and opioid-non-tolerant patients
The use of Durogesic in opioid-naïve patients has been associated with rare cases of significant respiratory depression and / or death when used in initial opioid therapy. There is a potential risk of severe or life-threatening hypoventilation although The lower dose of Durogesic is used as initial therapy in opioid-naive patients. Use of Durogesic is recommended in patients who have demonstrated opioid tolerance.
Respiratory Depression
As with all other potent opioids, significant respiratory depression may occur in some patients with Durogesic; patients should be monitored in case of onset of this effect. Respiratory depression may persist even after removal of the Durogesic transdermal patch. The incidence of this respiratory depression increases with increasing Durogesic dosage. CNS-active drugs can aggravate respiratory depression.
Addiction and potential for abuse
In the case of repeated administration of opioids, tolerance and physical and psychological dependence may develop. Iatrogenic addiction following opioid administration is rare.Patients with a previous history of drug addiction / alcohol abuse are more at risk of developing addiction and abuse following opioid treatment. Patients at increased risk of abuse can be treated appropriately with modified-release opioid formulations; however, such patients require monitoring for signs and symptoms of misuse, abuse or dependence.
Fentanyl can be subject to abuse in a similar way to other opioid agonists. Misuse or intentional misuse of Durogesic can result in overdose and / or death.
Children
Durogesic has not been studied in children less than 2 years of age. Durogesic should only be given to opioid-tolerant pediatric patients 2 years of age and older. Durogesic should not be given to children under 2 years of age. To prevent accidental ingestion by children, use caution when choosing the place of application of Durogesic and carefully check the adhesion of the patch.
Fever / exposure to external heat sources
As the temperature rises, more Durogesic can be released into the body. In case of fever it is therefore advisable to contact your doctor who will change the dosage of the drug if necessary. An increased release of Durogesic can also be the consequence of direct exposure to heat sources. Therefore, it is advisable to avoid heat pads, electric blankets, heated water beds, thermal and tanning lamps, intensive sun exposure, hot water bags, long hot water baths, saunas and hot thermal whirlpools during the treatment.
Transfer of the patch to another person
The patch should only be used on the skin of people for whom it has been prescribed by their doctor. There have been reports of accidental adhesion of a patch to a family member of a user due to close contact or sharing of the same bed. Sticking the patch to another person (especially a child) can cause an overdose. If the patch sticks to another person's skin, remove the patch immediately and contact your doctor.
Interactions Which drugs or foods may change the effect of Durogesic
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Report to the doctor the possible use of any drug or alcohol. The doctor will evaluate the opportunity to modify and / or suspend the therapy in progress.
Durogesic should not be taken with drugs that interfere with the metabolism of the active ingredient.
Combination of the following drugs with Durogesic may require additional monitoring and / or may require dose adjustment:
- drugs used in AIDS such as HIV protease inhibitors such as ritonavir and nelfinavir;
- some antibiotics such as clarithromycin, troleandomycin and rifampicin;
- some medications for the treatment of fungal infections such as ketoconazole, itraconazole, fluconazole and voriconazole;
- some drugs that affect the heart and circulatory system such as some calcium channel blockers (verapamil and diltiazem);
- some drugs to treat arrhythmias such as amiodarone;
- some medications to treat depression such as nefazodone;
- some drugs to treat seizures such as carbamazepine, phenobarbital and phenytoin.
Tell your doctor if you are being treated with any of these drugs.
- Durogesic should not be used with certain medications used for depression called monoamine oxidase inhibitors.
- Report to the doctor the possible use of central nervous system depressants (tranquilizers, hypnotics, antihistamines, sedatives, muscle relaxants, general anesthetics, opiates and phenothiazines), as their effects combined with those of Durogesic could cause drowsiness, hypoventilation, hypotension and deep sedation.
- Avoid the ingestion of alcohol and drugs while taking Durogesic, as the combined effects may also induce drowsiness.
- Durogesic should not be used with other opioid agonists or antagonists (such as buprenorphine, nalbuphine or pentazocine) because these drugs partially antagonize the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid-dependent patients.
Tell your doctor if you are using certain medications for depression known as Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) or Monoamine Oxidase Inhibitors (MAOIs). The prescribing physician should be aware of any use of these medicines because their combination with Durogesic may increase the risk of serotonin syndrome, a potentially life-threatening condition.
Warnings It is important to know that:
Durogesic is not indicated for the treatment of acute postoperative pain.
PATIENTS WHO HAVE MANIFESTED SERIOUS ADVERSE EVENTS SHOULD BE MONITORED FOR AT LEAST 24 HOURS AFTER STOPPING Durogesic.
Durogesic should not be used outside of the specific doctor's prescription. Durogesic must be kept out of the sight and reach of children (before and after use).
The Durogesic patch must not be cut. A patch that has been split, cut or damaged in any way should not be used.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
There are insufficient data on the use of Durogesic in pregnant women and therefore its reproductive toxicity is not known. Withdrawal syndrome has been reported in newborns by mothers taking chronic Durogesic during pregnancy. Therefore, in the event of pregnancy. Known or suspected, notify the doctor who will decide on the advisability of therapy with Durogesic. It is recommended not to use Durogesic during delivery as fentanyl crosses the placental barrier and may cause respiratory depression in the newborn.
The drug may be present in breast milk and can cause sedation and respiratory depression in the newborn and infant.
Breastfeeding should therefore be discontinued during treatment with Durogesic and for at least 72 hours after removal of the patch.
Tolerance
Long-term use of Durogesic can induce tolerance.
It is therefore possible that, during the course of therapy, the doctor may have to prescribe higher doses of the drug to achieve the same therapeutic effect.
Effects on ability to drive and use machines
Durogesic can interfere with the psycho-physical abilities necessary for carrying out potentially dangerous tasks that require special attention. Therefore, it is advisable to avoid driving vehicles or using machines unless otherwise instructed by your doctor.
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Dosage and method of use How to use Durogesic: Dosage
Adults
The dosage of Durogesic is decided by the doctor individually for each patient, according to his general condition, the intensity of the pain and the medications previously taken. Strictly follow the instructions of the doctor.
Children
Durogesic should only be given to opioid-tolerant pediatric patients (aged 2 to 16 years) who are already being treated with a dose equivalent to at least 30 mg of oral morphine per day.
Initial treatment with Durogesic
- Durogesic should be applied to a smooth part of the skin, trunk or forearms, not irritated, not irradiated and free from small wounds. A hairless surface is preferable or, if necessary, the application site should be shaved first using scissors (avoid using a razor, as it may irritate the skin).
- In young children, the preferred application site for Durogesic is the upper back in order to minimize the risk of the child taking it off.
- If the area where Durogesic is to be applied requires cleaning before applying the patch, this should be done with running water. Soaps, oils, lotions or any other agent that may irritate the skin or alter its characteristics should not be used. The skin must be perfectly dry before the patch is applied.
- Durogesic should be applied immediately after taking it out of the sealed pouch and removing the protective plastic layer. Avoid touching the sticky side of the patch. Visually inspect the patch to make sure it is not damaged. Do not use a patch that has been cut, split or damaged in any way.
- The patch should be pressed on the application site with the open palm of the hand for about 30 seconds, making sure that there is total contact especially around the edges.
- After application, wash your hands with running water (without soap).
- Durogesic must be worn continuously for 3 days (72 hours) during which time you can bathe, shower or swim.
- To facilitate the correct use of Durogesic, a space is provided on the packaging to record the date and time of application of each new patch.
Patch replacement
- After 3 days, peel off the patch by lifting one end. Exceptionally, the patch may come off on its own.
- Before throwing away the used patch, fold it so that the adhesive part closes on itself and discard it as indicated by the procedures for the disposal of drugs.
- Then immediately apply a new patch in a different place than the previous one. Avoid applying a new patch to the same area for several days.
- Follow the instructions for "Initial treatment with Durogesic".
Useful information
- The therapeutic effect of the first Durogesic patch may occur with some delay (24 hours) from the time of application as the drug must first be absorbed from the epidermis. Other analgesic drugs may therefore be needed during the first 24 hours.
- If the pain returns, tell your doctor who will adjust your Durogesic dosage and / or prescribe other pain relievers as well.
- Talk to your doctor if you (or a member of your family) have abused or been addicted to alcohol, medicines or illegal drugs.
Never change the dosage of the drug, or interrupt therapy, without specific instructions from the doctor.
Overdose What to do if you have taken too much Durogesic
In case of accidental ingestion / intake of an excessive dose of Durogesic, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Durogesic, ask your doctor or pharmacist.
Symptoms
The most important manifestation of overdose is respiratory depression.
In the event that a patient treated with Durogesic breathes abnormally, slowly or weakly, remove the patch and notify the doctor immediately. In the meantime, keep the patient awake by talking to him and / or shaking him from time to time.
Urgent measures
Inject naloxone and hospitalize the patient.
IF IN ANY DOUBT ABOUT USING Durogesic, ASK YOUR DOCTOR OR PHARMACIST
Side Effects What are the side effects of Durogesic
Like all medicines, Durogesic can cause side effects, although not everybody gets them.
The following side effects may occur when taking this medicine:
Adult Patients
Very common side effects (reported by at least 1 in 10 patients):
- headache, dizziness, sleepiness;
- nausea and vomit;
- constipation.
Common side effects (reported by at least 1 in 100 but less than 1 in 10 patients):
- lack or reduction of appetite;
- hypersensitivity;
- confusion, sensation of seeing, hearing, noticing odors, sensations or tastes that are not present;
- dizziness;
- anxiety, feeling sad or depressed;
- trouble falling asleep or staying awake, shaking, tingling sensation;
- feeling of heartbeat, fast heartbeat;
- high blood pressure;
- dry mouth, indigestion, stomach upset, stomach pain, diarrhea;
- itching, redness of the skin, skin rash, excessive sweating, hives;
- involuntary muscle movements including muscle spasms;
- tiredness, weakness, generally feeling unwell or restless, feeling cold, swelling of the feet, ankles and hands;
- inability to urinate;
- feeling short of breath.
Uncommon side effects (reported by at least 1 in 1,000 but less than 1 in 100 patients):
- euphoria, agitation, disorientation;
- decreased sensitivity (especially tactile, thermal and pain), memory loss, seizures (also called convulsions);
- muscle twitching;
- slow heart rate, bluish discoloration of the skin;
- low blood pressure;
- difficulty, even severe, in breathing;
- intestinal blockage;
- inflammation of the skin or rash caused by contact with something the person is allergic to, difficulty in any phase of normal sexual response (desire, arousal or orgasm), inability to get or maintain an erection;
- application site reaction (including allergic reaction), feeling both hot and cold; flu-like syndrome, unpleasant symptoms that occur after stopping the drug or when the dose is decreased;
- fever;
- reduced level of consciousness;
- loss of consciousness;
- blurred vision.
Rare side effects (reported by at least 1 in 10,000 patients but less than 1 in 1,000 patients):
- narrowing of the pupil;
- partial intestinal obstruction;
- dermatitis and eczema at the application site;
- inability to breathe, reduction in the amount of air entering the lungs.
Not known: frequency cannot be estimated from the available data
- severe allergic reactions sufficient to cause wheezing, difficulty breathing and very low blood pressure which could be life-threatening;
- very slow breathing rhythm.
- Important additional information
- Like other pain relievers of the same class, Durogesic can cause respiratory depression. If a patient treated with Durogesic breathes slowly or too weakly, remove the patch, notify the doctor immediately and keep the patient awake (by talking to him and / or shaking him from time to time).
- Drugs such as Durogesic can be addictive. However, this is unlikely to occur if the drug is used correctly.
- Abrupt discontinuation of long-term treatment of Durogesic may lead to withdrawal symptoms such as: nausea, vomiting, diarrhea, anxiety, sweating. The decision to discontinue treatment should be made with your doctor. If your doctor decides to stop treatment. to suspend the treatment the patient must carefully follow all his instructions.
- Similar side effects can occur when other opioid analgesics are replaced with Durogesic. The patient should inform the doctor if these side effects occur.
Pediatric patients
Very common adverse events reported in pediatric clinical trials were fever, vomiting, nausea, headache, constipation and diarrhea.
There have been very rare reports of newborns with neonatal discontinuation syndrome if the mother was on chronic Durogesic therapy during pregnancy (see section "Pregnancy and lactation").
Very common side effects (reported by at least 1 in 10 patients):
- headache;
- vomiting, nausea, constipation, diarrhea;
- itch.
Common side effects (reported by at least 1 in 100 but less than 1 in 10 patients):
- hypersensitivity;
- anorexia;
- insomnia, anxiety, depression, hallucinations;
- somnolence, dizziness, tremor, hypoesthesia;
- respiratory depression;
- abdominal pain, upper abdominal pain, dry mouth;
- rash, hyperhidrosis, erythema;
- urinary retention;
- peripheral edema, fatigue, application site reaction, asthenia.
Uncommon side effects (reported by at least 1 in 1,000 but less than 1 in 100 patients):
- confusional state;
- paraesthesia;
- miosis;
- vertigo;
- cyanosis;
- contact dermatitis, skin diseases, allergic dermatitis, eczema;
- withdrawal syndrome, flu-like illness;
- muscle contractions.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored. Warning: Do not use the medicine after the expiry date stated on the package.
Do not use the patch if the bag containing it is not well sealed and intact.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep used and unused Durogesic patches out of the sight and reach of children.
Handling of the patch
Used patches should be folded so that the sticky part of the patch adheres to itself and then they should be discarded safely. Accidental exposure to used and unused patches can cause fatal outcome especially in children.
Unused patches must be returned to the pharmacy (hospital).
COMPOSITION
Durogesic 12 micrograms / hour transdermal patch
Active principle: fentanyl 2.1 mg on an area of 5.25 cm2
Excipients: polyethylene terephthalate / ethyl-vinyl acetate film, polyacrylate adhesive, orange ink, siliconized polyester film.
Durogesic 25 micrograms / hour transdermal patch
A transdermal patch contains:
Active principle: fentanyl 4.2 mg on a surface of 10.5 cm2
Excipients: polyethylene terephthalate / ethyl-vinyl acetate film, polyacrylate adhesive, red ink, siliconized polyester film.
Durogesic 50 micrograms / hour transdermal patch
A transdermal patch contains:
Active principle: fentanyl 8.4 mg on a surface of 21 cm2
Excipients: polyethylene terephthalate / ethyl-vinyl acetate film, polyacrylate adhesive, green ink, siliconized polyester film.
Durogesic 75 micrograms / hour transdermal patch
A transdermal patch contains:
Active principle: fentanyl 12.6 mg on a surface of 31.5 cm2
Excipients: polyethylene terephthalate / ethyl-vinyl acetate film, polyacrylate adhesive, blue ink, siliconized polyester film.
Durogesic 100 micrograms / hour transdermal patch
A transdermal patch contains:
Active principle: fentanyl 16.8 mg on an area of 42 cm2
Excipients: polyethylene terephthalate / ethyl-vinyl acetate film, polyacrylate adhesive, gray ink, siliconized polyester film.
PHARMACEUTICAL FORM AND CONTENT
Rectangular transdermal patches with continuous drug release into the bloodstream within 72 hours after application.
Durogesic is available in five different strengths:
Durogesic 12 micrograms / hour transdermal patch - orange box containing 3 matrix transdermal patches
Durogesic 25 micrograms / hour transdermal patch - pink box containing 3 matrix transdermal patches
Durogesic 50 micrograms / hour transdermal patch - green box containing 3 matrix transdermal patches
Durogesic 75 micrograms / hour transdermal patch - blue box containing 3 matrix transdermal patches
Durogesic 100 micrograms / hour transdermal patch - gray box containing 3 matrix transdermal patches
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
DUROGESIC
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
DUROGESIC 12 mcg / hour transdermal patch
A transdermal patch contains:
Active ingredient: 2.1 mg fentanyl
DUROGESIC 25 mcg / hour transdermal patch
A transdermal patch contains:
Active ingredient: fentanyl 4.2 mg
DUROGESIC 50 mcg / hour transdermal patch
A transdermal patch contains:
Active ingredient: 8.4 mg fentanyl
DUROGESIC 75 mcg / hour transdermal patch
A transdermal patch contains:
Active ingredient: fentanyl 12.6 mg
DUROGESIC 100 mcg / hour transdermal patch
A transdermal patch contains:
Active ingredient: fentanyl 16.8 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Rectangular transdermal patch with continuous systemic release within 72 hours after application.
DUROGESIC is available in five different strengths:
- 5.25 cm2 patch containing 2.1 mg fentanyl released at the rate of 12.5 mcg / hour
- 10.5 cm2 patch containing 4.2 mg of fentanyl released at the rate of 25 mcg / hour
- 21 cm2 patch containing 8.4 mg of fentanyl released at a rate of 50 mcg / hour
- 31.5 cm2 patch containing 12.6 mg fentanyl released at the rate of 75 mcg / hour
- 42 cm2 patch containing 16.8 mg of fentanyl released at the rate of 100 mcg / hour
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults:
DUROGESIC is indicated for the treatment of chronic pain from cancer and pain of rebellion that requires opiate-based analgesia.
Children:
DUROGESIC is indicated for the long-term treatment of severe pain in children from 2 years of age who are already being treated with opioids.
04.2 Posology and method of administration
The dosage of DUROGESIC should be individualized according to the patient's condition and should be checked at regular intervals after application.
Choice of starting dosage:
The appropriate dosage to be used at the initiation of DUROGESIC therapy should be based on the patient's experience with opioids. The use of DUROGESIC in opioid-tolerant patients is recommended. Other factors that must be considered are the patient's general and medical condition, including weight, age and degree of debilitation, as well as the degree of opioid tolerance.
Adults
Opioid-tolerant patients
For dosing in opioid-tolerant patients transitioning from oral or parenteral opioid treatment to DUROGESIC treatment, refer to the Equianalgesic Efficacy Conversion table below. The dosage can then be titrated with increases or decreases, if required, with variations of 12 or 25 mcg / hour in order to reach the most appropriate minimum dose of DUROGESIC based on the response and additional analgesic needs.
Opiate-naïve patients
Clinical experience with DUROGESIC is limited in opioid-naive patients. If therapy with DUROGESIC is considered appropriate in opioid-naive patients, it is recommended that such patients be titrated with the lowest dose of immediate-release opioids (such as morphine, hydromorphone). , oxycodone, tramadol and codeine) in order to achieve the equianalgesic dose relative to DUROGESIC with a release of 25 mcg / hour.These patients can then be given DUROGESIC 25 mcg / hour.
The dosage may subsequently be titrated with increases or decreases, if required, with variations of 12 or 25 mcg / hour in order to reach the most appropriate minimum dose of DUROGESIC based on the response and additional analgesic needs (see Efficacy Conversion table. Equianalgesic and section 4.4 "Special warnings and precautions for use").
Conversion of Equianalgesic Efficacy
1. Calculate the analgesic dose for the previous 24 hours.
2. Convert the resulting amount to the equianalgesic dose of morphine using Table 1. All IM or oral doses in this table are considered equivalent in analgesic effect to 10 mg IM morphine.
3. To derive the dose of DUROGESIC corresponding to the calculated 24 hour morphine dose, use Table 2 or Table 3 of dose conversion as described below:
to. Table 2 indicates doses for adult patients requiring alternation or conversion from another opioid (conversion ratio of oral morphine to transdermal fentanyl is approximately 150: 1).
b. Table 3 indicates doses for adult patients who are on stable and well tolerated opioid therapy (conversion ratio of oral morphine to transdermal fentanyl is approximately 100: 1).
Table 1: Equianalgesic Efficacy Conversion Table (#)
* Based on single dose studies in which an IM dose of each of the listed drugs was compared to morphine to establish relative potency. Oral doses are those recommended in case of a change from parenteral to oral route.
** The oral potency / MI ratio of 1: 3 for morphine is based on clinical experience in patients with chronic pain.
(#) Ref .: Modified by Foley K.M. The treatment of cancer pain. NEJM 1985; 313: 84-95.
Table 2: Recommended starting dosage of DUROGESIC based on the oral daily dose of morphine
In clinical trials these oral daily dose ranges of morphine were used as a basis for conversion to DUROGESIC treatment.
Table 3: Recommended starting dose of DUROGESIC based on daily oral morphine dose (for adult patients who are on stable and well tolerated opioid therapy)
The initial assessment of the maximum analgesic effect of DUROGESIC cannot be made earlier than 24 hours after application of the patch, as the plasma concentration of fentanyl gradually increases over the 24 hours following the first application of the transdermal patch.
Previous analgesic therapies should therefore be phased out after application of the first transdermal patch until the analgesic efficacy of DUROGESIC is achieved.
It should be emphasized that this table only applies for the conversion of the recommended dosage between orally administered morphine (or its equivalent) and the DUROGESIC patch and should not be used for the conversion between DUROGESIC and other opioids as overdose may occur.
In the first 24 hours, the analgesic effect of the first dose of the DUROGESIC patch will not be optimal. Therefore, during the first 12 hours after administration of DUROGESIC, the patient should be given the usual dose of analgesic. In the remaining 12 hours the dose. of analgesic should be administered according to needs assessed on a clinical basis.
Since the plasma concentration of fentanyl gradually increases over the range of 12 to 24 hours, it is recommended that the patient be monitored for the evaluation of side effects that may occur (including hypoventilation) in the first 48 hours after the start of the treatment. therapy with DUROGESIC or during titration to achieve the optimal dose (see Section 4.4 Special warnings and special precautions for use).
Determination of the Titration Posology and Maintenance Therapy
A 12 mcg / hour patch of DUROGESIC is available for dose adjustment. DUROGESIC must be replaced every 72 hours. The posology must be determined individually until a balance is achieved between analgesic efficacy and tolerability. If analgesia is insufficient after the initial application, the dose can be increased after 3 days. Further dose adjustments can be made at 3-day intervals thereafter. At the start of therapy (first application or possibly second application), some patients may not achieve "adequate analgesia by the third day using the recommended interval between applications of 72 hours (before patients have reached steady state. ) and may require the DUROGESIC patch to be changed every 48 hours instead of every 72 hours. Reduction of the duration of applications aims at achieving greater analgesia in the short term commensurate with the increase in serum concentration of fentanyl (see section 5.2 Pharmacokinetic properties). Dosage should normally be adjusted in increments of 12 or 25 micrograms / hour at a time. , although the additional analgesics needed (oral morphine 90 mg / day ≈ DUROGESIC 12/25 mcg / hour) and the extent of the patient's pain should be taken into account. More than one DUROGESIC patch can be used at a time for doses above 100 mcg / hour. Patients may periodically need supplemental doses of a short-acting analgesic for transient painful exacerbations. Some patients may need to resort to additional or alternative methods of opioid administration when the dose of DUROGESIC exceeds 300 mcg / hour.
Pediatric population
Children aged 16 years and over: follow the recommended posology for adults.
Children aged 2-16 years:
Dosage
DUROGESIC should only be given to opioid-tolerant pediatric patients (ages 2-16 years) who are already being treated with a dose equivalent to at least 30 mg of oral morphine per day. For conversion of pediatric patients from oral or parenteral opioid treatment to treatment with DUROGESIC, refer to the Conversion of Equianalgesic Efficacy Sheet (Table 1) and the recommended dosage of DUROGESIC based on the oral daily dose of morphine (Table 4) .
Clinical studies currently available report only limited information for children receiving more than 90 mg of morphine per day orally. In pediatric studies, the daily dose required for the fentanyl transdermal patch was calculated very carefully: 30 - 44 mg morphine per day orally or the equivalent opioid dose was replaced by a 12 mcg / DUROGESIC transdermal patch. h.
If the analgesic effect of DUROGESIC is insufficient, a supplemental dose of morphine or a short-acting analgesic should be given. Depending on the requirement for the additional analgesic dose and the child's distress, a decision may be made to use more patches. L "Dose adjustment should be achieved in 12 mcg / hour increments.
Table 4: Recommended starting dosage of DUROGESIC based on oral daily dose of morphine in pediatric patients
Conversion to DUROGESIC treatment at doses above 25 mcg / h is the same for adult patients (See Table 2).
Discontinuation of DUROGESIC therapy
If discontinuation of DUROGESIC therapy is necessary, its substitution with other opioid drugs should be gradual starting with a low dose to be progressively increased. In fact, plasma levels of fentanyl gradually decrease after removal of DUROGESIC, it takes 17 hours or more. plus because the plasma concentration of fentanyl decreases by 50%.
In general, discontinuation of opioid-type analgesia should be gradual in order to prevent the onset of opioid withdrawal syndrome. Symptoms of this syndrome (see section 4.8 Undesirable effects) may arise in some patients after conversion or dose adjustment. Table 2 and Table 3 should not be used to convert from DUROGESIC to other therapies to avoid overestimating the new one. analgesic dose and potentially cause overdose.
Method of administration
DUROGESIC should be applied to a smooth, clean, dry tract of non-irritated, non-irradiated skin of the trunk or forearms.
It is preferable to apply the transdermal patch on a hairless surface, or, if necessary, to perform a trichotomy avoiding the use of the razor on the application site.
In young children, the preferred application site for DUROGESIC is the upper back in order to minimize the risk of the child taking it off.
If the point where DUROGESIC is to be applied requires cleaning before application, this should be done with running water. Soaps, oils, lotions or any other agent that may irritate the skin or alter its characteristics should not be used. The skin must be perfectly dry before the transdermal system is applied.
DUROGESIC must be applied immediately after having removed it from the sealed wrapping. After removing the 2 parts of the protective layer that cover the adhesive part, the transdermal patch must be pressed on the application site with the open palm of the hand for about 30 seconds, making sure that the contact is total especially around the edges.
DUROGESIC must be worn continuously for 72 hours. Each new transdermal patch should be applied to a different point from the previous one, after having peeled off and removed the last one. It is best to avoid applying a new patch to the same area for several days.
04.3 Contraindications
DUROGESIC is contraindicated in patients with known hypersensitivity to fentanyl or to any of the excipients present in the patch.
DUROGESIC is contraindicated in acute or postoperative pain therapy because dose titration in short-term therapy is not possible with consequent risk of severe or life-threatening hypoventilation.
DUROGESIC is generally contraindicated in pregnancy.
DUROGESIC is contraindicated during breastfeeding.
DUROGESIC is contraindicated in cases of severe respiratory depression.
04.4 Special warnings and appropriate precautions for use
PATIENTS WHO HAVE MANIFESTED SERIOUS ADVERSE EVENTS SHOULD BE MONITORED FOR AT LEAST 24 HOURS OR MORE "AFTER DUROGESIC IS DISCONTINUED, BASED ON CLINICAL SYMPTOMS, BECAUSE PLASMA CONCENTRATIONS OF ABOUT 50% FENTANUIL DROP 17 HOURS (13 TO 22 HOURS).
DUROGESIC must be kept out of the reach and sight of children (before and after use).
The DUROGESIC patch must not be cut. A patch that has been split, cut or damaged in any way should not be used
Opioid-naïve patients and opioid-non-tolerant patients
The use of DUROGESIC in opioid-naive patients has been associated with rare cases of significant respiratory depression and / or death when used in initial opioid therapy. There is a potential risk of severe or life-threatening hypoventilation although The lowest dose of DUROGESIC is used as initial therapy in opioid-naive patients. The use of DUROGESIC in patients who have demonstrated opioid tolerance is recommended (see section 4.2 "Posology and method of administration, Choice of starting dosage: Adults" ).
Respiratory Depression
As with all other potent opioids, significant respiratory depression may occur in some patients with DUROGESIC; patients should be monitored in case of onset of this effect. Respiratory depression may persist even after removal of the DUROGESIC transdermal patch. The incidence of such respiratory depression increases with increasing DUROGESIC dosage (see section 4.9 "Overdose" regarding respiratory depression). CNS-active drugs may aggravate respiratory depression (see section 4.5 "Interactions with other medicinal products and other forms of interaction").
Chronic Lung Diseases
The most serious side effects can occur in patients with chronic lung disease, whether obstructive or otherwise. Indeed, in such patients, opiates can reduce respiratory rate and increase airway resistance.
Addiction and potential for abuse
In the case of repeated administration of opioids, tolerance and physical and psychological dependence may develop. Iatrogenic addiction following opioid administration is rare.
Patients with a previous history of drug addiction / alcohol abuse are more at risk of developing addiction and abuse following opioid treatment. Patients at increased risk of abuse can be treated appropriately with modified-release opioid formulations; however, such patients require monitoring for signs and symptoms of misuse, abuse or dependence.
Fentanyl can be subject to abuse in a similar way to other opioid agonists. Intentional abuse or misuse of DUROGESIC can result in overdose and / or death.
Intracranial hypertension
DUROGESIC should be used with caution in patients who may be particularly sensitive to the intracranial effects of CO2 retention, such as those with signs of increased intracranial pressure, impaired consciousness or coma. DUROGESIC should be used with caution in patients with brain tumors.
Heart Diseases
Fentanyl can produce bradycardia and should therefore be administered with caution in patients suffering from bradyarrhythmia.
Opiates can cause hypotension, especially in patients with acute hypovolaemia. Symptomatic hypotension and / or underlying hypovolaemia should be corrected prior to initiation of treatment with transdermal fentanyl patches.
Hepatic insufficiency
Since fentanyl is metabolised to inactive metabolites in the liver, liver failure may delay its elimination. If patients with hepatic insufficiency are being treated with DUROGESIC they should be monitored closely for symptoms of fentanyl toxicity and the dosage of DUROGESIC should be reduced if necessary (see section 5.2 "Pharmacokinetic properties").
Kidney failure
Less than 10% of fentanyl is excreted unchanged via the kidney and, unlike morphine, there are no known active metabolites in renal elimination. Data obtained after intravenous administration of fentanyl in patients with renal insufficiency suggest that the volume distribution of fentanyl can be changed by dialysis and this may affect plasma concentrations. If DUROGESIC is to be administered to patients with renal insufficiency, they should be closely monitored for symptoms of fentanyl toxicity and the dosage of DUROGESIC should be reduced if necessary (see section 5.2 "Pharmacokinetic properties").
Fever / exposure to external heat sources
A pharmacokinetic model suggests that fentanyl serum concentrations can increase by about one third if body temperature reaches 40 ° C. Therefore, patients with fever should be monitored for opioid drug side effects and the dose of DUROGESIC should be adjusted if necessary.
With increasing temperature there may be a potential increase in fentanyl released from the system and this could lead to possible overdose and death. A clinical pharmacology study performed in healthy adult subjects demonstrated that applying heat to DUROGESIC patches resulted in an increase in the mean AUC values of fentanyl by 120% and the mean C values by 61%.
All patients should be advised to avoid exposure of the DUROGESIC application site to direct external heat sources such as heating pads, electric blankets, heated water beds, thermal and tanning lamps, intensive sun exposure, hot water bags, long baths. in hot water, saunas and hot thermal whirlpools.
Serotonin syndrome
Caution is advised when DUROGESIC is co-administered with drugs affecting the serotonergic transmission systems.
The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic medicinal products such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) and certain drugs that alter the metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]) Serotonin syndrome can occur at recommended doses.
Serotonin syndrome may include changes in mental status (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, unstable blood pressure, hyperthermia), neuromuscular changes (e.g. hyperreflexia, incoordination, rigidity) and / or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).
If serotonin syndrome is suspected, treatment with DUROGESIC should be discontinued
Interactions with other medicines
Interactions with CYP3A4 inhibitors
Concomitant use of DUROGESIC with cytochrome P450 3A4 (CYP3A4) inhibitors (eg ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem and amiodarone concentrations may cause increased plasma concentrations) lead to an increase or prolongation of both therapeutic effects and adverse events and can cause severe respiratory depression. Special patient care and observation are appropriate in this situation. Hence, concomitant use of transdermal fentanyl and cytochrome CYP3A4 is not recommended unless the patient is closely monitored. Patients, especially those receiving administration of DUROGESIC and CYP3A4 inhibitors, should be monitored for signs of respiratory depression and, if justified, dose adjustments made.
Accidental exposure by patch transfer
Accidental transfer of a fentanyl patch to the skin of a person who is not using the patch (particularly a child), while sleeping in the same bed or in close physical contact, can result in an opiate overdose for the person does not use the patch. Patients should be advised that should a patch transfer occur, the transferred patch should be removed immediately from the skin of the non-user (see section 4.9 "Overdose").
Use in Elderly Patients
Results from intravenous studies with fentanyl suggest that elderly patients may have a lower elimination capacity, a prolonged "drug half-life, and" greater drug hypersensitivity than younger patients. Elderly patients receiving DUROGESIC should be closely monitored for symptoms of fentanyl toxicity and the DUROGESIC dosage should be reduced if necessary (see section 5.2 "Pharmacokinetic properties").
Use in Pediatric Patients
DUROGESIC should not be administered to opioid-naive pediatric patients (see section 4.2 Posology and method of administration). There is a potential for serious or life-threatening hypoventilation, regardless of the dose of the DUROGESIC transdermal patch administered (see Table 1 and 2 in section 4.2, Posology and method of administration).
DUROGESIC has not been studied in children less than 2 years of age. DUROGESIC should only be administered to opioid-tolerant pediatric patients 2 years of age and older (see section 4.2 Posology and method of administration). DUROGESIC should not be given to children under 2 years of age.
To prevent accidental ingestion by children, use caution when choosing the place of application of DUROGESIC (see section 4.2 Posology and method of administration) and carefully monitor the adhesion of the patch.
Gastrointestinal tract
Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. The resulting prolongation of gastrointestinal transit time may be responsible for constipation caused by fentanyl. Patients should be informed about measures to prevent constipation and the use of prophylactic laxative therapy should be considered. Exercise caution in patients with chronic constipation. If paralytic ileus is known or suspected. , treatment with DUROGESIC should be discontinued.
Feeding time
Since fentanyl is excreted in breast milk, breastfeeding should be discontinued during treatment with Durogesic (see also section 4.6).
Patients with myasthenia gravis
Non-epileptic (myo) clonic reactions may occur. Caution should be used when treating patients with myasthenia gravis.
Concomitant use of mixed agonists / antagonists
The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended (see also section 4.5).
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant use of other central nervous system depressants, including opiates, sedatives, hypnotics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, sedative antihistamines, and alcoholic beverages, may produce additional depressant effects; Hypoventilation, hypotension and profound sedation, coma or death may occur. Therefore, the concomitant use of any of these drugs and DUROGESIC requires special attention and monitoring of the patient.
Fentanyl, a high-clearance drug, is rapidly metabolised primarily by cytochrome CYP3A4.
Interactions with CYP3A4 inhibitors
Concomitant use of trans dermal fentanyl and cytochrome P4503A4 (CYP3A4) inhibitors (eg ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapzamil plasma concentration of fentanyl, with consequent possible increase or prolongation of both the therapeutic and unwanted effects and could cause severe respiratory depression. In this case, the patient should be subjected to careful treatment and surveillance. The concomitant use of cytochrome inhibitors CYP3A4 and transdermal fentanyl is not recommended, unless the patient is carefully monitored (see section 4.4 "Special warnings and precautions for use").
Interactions with inducers of cytochrome CYP3A4
Concomitant use of inducers of cytochrome CYP3A4 (eg rifampicin, carbamazepine, phenobarbital, phenytoin) may lead to decreased plasma concentrations of fentanyl and decreased therapeutic effect. This may require a dose adjustment of transdermal fentanyl. After discontinuation of treatment with cytochrome CYP3A4 inducers, the effects caused by induction gradually diminish and may lead to increased plasma concentrations of fentanyl which may increase or prolong both therapeutic and undesirable effects and may cause severe respiratory depression. In this case, careful monitoring and dose adjustment should be performed if warranted.
Monoamine oxidase inhibitors (MAOIs)
The use of DUROGESIC is not recommended in patients requiring concomitant administration of monoamine oxidase inhibitors (MAOIs). Serious and unpredictable interactions with monoamine oxidase inhibitors (MAOIs) including potentiation of opiate effects or serotonergic effects have been reported. Therefore DUROGESIC should not be used within 14 days following discontinuation of monoamine oxidase inhibitor (MAOI) therapy.
Concomitant use of mixed agonists / antagonists
Concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. These drugs have a "high affinity for opioid receptors with a relatively low intrinsic activity" therefore partially antagonize the analgesic effect of fentanyl and may induce withdrawal symptoms in patients. opioid tolerant (see also section 4.4).
Serotonergic medicines
Co-administration of fentanyl with serotonergic agents, such as a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-Noradrenaline Reuptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI) may increase the risk of serotonin syndrome, a potentially life-threatening condition.
04.6 Pregnancy and lactation
There are insufficient data on the use of DUROGESIC in pregnant women. Animal studies have shown some reproductive toxicity (see section 5.3 "Preclinical safety data"). The potential risk in humans is unknown although fentanyl, used for intravenously as an anesthetic, has been shown to cross the placental barrier in the early stages of pregnancy. Discontinuation syndrome has been reported in infants born to mothers on chronic DUROGESIC therapy during pregnancy. It is recommended not to use DUROGESIC during pregnancy unless absolutely necessary.
The use of DUROGESIC during childbirth is not recommended as fentanyl cannot be used in the treatment of acute or post-operative pain (see section 4.3 "Contraindications").
Also, as fentanyl crosses the placental barrier, the use of DUROGESIC during delivery can cause respiratory depression in the newborn.
Fentanyl is excreted in breast milk and can cause sedation and respiratory depression in the nursing infant. Breastfeeding should therefore be discontinued during treatment with DUROGESIC and for at least 72 hours after removal of the patch.
04.7 Effects on ability to drive and use machines
DUROGESIC can interfere with the psycho-physical abilities necessary for carrying out potentially dangerous tasks that require special attention, such as driving a car or using machinery.
04.8 Undesirable effects
The safety of DUROGESIC was evaluated in 1854 adult and pediatric patients who participated in 11 clinical trials (double-blind [Durogesic with placebo or active control] and / or open label [Durogesic with no control or active control]) in the treatment chronic cancer and non-cancer pain. The analysis of these patients who received at least 1 dose of DUROGESIC provided safety data. Based on the safety data collected from the analysis of these clinical trials, the most commonly reported adverse drug reactions (ADRs) were (≥10% incidence rate): nausea (35.7%), vomiting (23.2%), constipation (23.1%), somnolence (15.0%), dizziness (13.1%) and headache (11.8%).
Adverse reactions (ADRs) reported with the use of DUROGESIC in clinical trials, including the adverse reactions listed above, and from post-marketing experience are listed below.
Frequencies are reported according to the following convention: Very common (≥1 / 10); Common (≥1 / 100,
Like other opioid analgesics, prolonged use of DUROGESIC may develop tolerance, physical and psychological dependence (see section 4.4. Special warnings and precautions for use).
Symptoms of opioid withdrawal syndrome (such as nausea, vomiting, diarrhea, anxiety and chills) may occur in some patients following conversion of previous opioid treatment to DUROGESIC, or abrupt discontinuation of therapy. of the dosage may attenuate the intensity of the symptoms of the withdrawal syndrome (see section 4.2 "Posology and method of administration"). There have been very rare reports of newborns with neonatal discontinuation syndrome when the mother was on chronic therapy with DUROGESIC during pregnancy (see section 4.6 "Pregnancy and lactation").
Pediatric patients
The adverse event profile in children and adolescents treated with DUROGESIC is similar to that seen in adults. No risks have been identified in the pediatric population other than those anticipated with the use of opioids for the treatment of pain associated with serious illness and there appears to be no specific risk associated with the use of DUROGESIC in children aged two and above. years when used as directed.
Very common adverse events reported in pediatric clinical trials were fever, vomiting and nausea.
The safety of DUROGESIC was evaluated in 289 pediatric patients (
Based on pooled safety data from these 3 clinical trials in pediatric patients, the most commonly reported adverse drug reactions were (≥10% incidence rate): vomiting (33.9%), nausea (23.5%) ). headache (16.3%), constipation (13.5%), diarrhea (12.8%) and itching (12.8%). Table B shows all ADRs reported in pediatric patients treated with DUROGESIC in the previously mentioned clinical studies.
The ADRs for the pediatric population reported in Table B were assigned to frequency categories using the same convention used for Table A.
04.9 Overdose
Symptoms
Fentanyl overdose manifests itself as an enhancement of its pharmacological actions. The most serious effect is respiratory depression.
Treatment
For the management of respiratory depression, immediate countermeasures include removal of the DUROGESIC trans dermal patch and physical or verbal stimulation of the patient. These actions can be followed by the administration of a specific opiate antagonist, such as naloxone. Respiratory depression due to overdose may have a longer duration than the opioid antagonist itself. The interval between intravenous antagonist administrations should be chosen with particular care, given the possibility of "re-narcotization" once the transdermal patch has been removed; repeated administration or continuous infusion of naloxone may be required. Reversing the narcotic effect can result in acute onset of pain and release of catecholamines.
If the clinical situation justifies it, a patency of the airways must be established and maintained, possibly via the oropharynx or with an endotracheal cannula; Oxygen should be administered and respiration assisted or controlled as needed. Adequate body temperature and water balance should be maintained. Should severe or persistent hypotension arise, the possibility of hypovolaemia should be considered and the condition should be treated with "adequate fluid parenteral therapy."
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Opioids. Phenylpiperidine derivatives.
ATC code: N02AB03
Fentanyl is an opioid analgesic which interacts predominantly with µ-opiate receptors. Its main therapeutic actions are analgesia and sedation. The minimum plasma concentrations necessary for the analgesic action of fentanyl in patients not addicted to opiate substances are between 0.3 and 1.5 ng / ml; the frequency of undesirable effects increases with plasma concentrations above 2 ng / ml. Both the trough effective concentration and the plasma concentration at which opioid-related adverse reactions occur increase with repeated patient exposure to the drug.
The emergence of drug tolerance presents a considerable interindividual variability.
The safety profile of DUROGESIC was evaluated in three "open-label studies" involving 293 pediatric patients with chronic pain, in an age group between 2 and 18 years, including 66 with an "age of 2 and age 6. In these studies, the oral daily dose of 30-45 mg morphine was replaced by a 12 mcg / h DUROGESIC transdermal patch.
Initial doses of 25 mcg / h and even higher doses were administered to 181 patients who had previously been treated with a daily dose of at least 45 mg of morphine orally.
05.2 Pharmacokinetic properties
Absorption
DUROGESIC allows continuous systemic release of fentanyl throughout the 72 hour application period. Fentanyl is released at a relatively constant rate. The concentration gradient existing between the release membrane and the epidermal layers leads to the diffusion of fentanyl.
After an initial application of DUROGESIC, plasma concentrations of fentanyl gradually increase, generally leveling off between 12 and 24 hours and remaining relatively constant for the remainder of the 72 hour application.
Plasma concentrations of fentanyl are proportional to the size of the patch used. At the end of the second application lasting 72 hours, the steady-state plasma concentration is reached which is maintained during subsequent applications of a patch of the same size.
A pharmacokinetic model has suggested that fentanyl serum concentrations may increase by 14% (range 0 - 26%) if a new patch is applied after 24 hours instead of the recommended application after 72 hours.
Distribution
Plasma protein binding of fentanyl is approximately 84%.
Metabolism
Fentanyl is a high clearance drug and is rapidly and extensively metabolised, primarily by cytochrome CYP3A4, in the liver.
The main metabolite, norfentanil, is inactive. The skin does not appear to metabolize transdermally released fentanyl. This was determined through a human keratocytic cell test and clinical studies in which 92% of the dose released from the patch was considered to be unchanged fentanyl appearing in the systemic circulation.
Elimination
Once DUROGESIC is removed, plasma concentrations of fentanyl gradually decline to approximately 50% in approximately 17 hours (13 to 22 hours) after a 24-hour dosing. After a 72-hour administration, the mean half-life ranges from 20 to 27 hours. The continuous transdermal absorption of fentanyl causes a slower disappearance of the drug from the serum than after intravenous infusion, in which the apparent half-life is of about 7 hours (3 to 12 hours).
Within 72 hours of intravenous fentanyl administration, 75% of the fentanyl dose is excreted in the urine, mostly as metabolites, with less than 10% as unchanged drug. Approximately 9% of the dose is recovered in the faeces, mainly in the form of metabolites.
Special populations
Senior citizens
Data from studies with intravenous fentanyl suggest that elderly patients may have reduced clearance, a prolonged half-life and may be more sensitive to the drug than young patients. In a study conducted with DUROGESIC, healthy elderly subjects exhibited a pharmacokinetics of fentanyl which were not significantly different from young subjects although peak plasma concentrations tended to be lower and mean half-life values were prolonged to approximately 34 hours. Elderly patients should be carefully monitored for signs of fentanyl toxicity and dose. it should be reduced if necessary (see section 4.4 "Special warnings and precautions for use").
Pediatric patients
The clearance (L / h / kg) in pediatric patients, adjusted for body weight, was 82% higher in children in the 2-5 year age group and 25% higher for those aged 2-5 years. between 6 and 10 years compared to the clearance of children aged between 11 and 16 who, on the other hand, showed values equal to those of adults.
These conclusions were taken into account in determining the recommended dose in pediatric patients.
Hepatic insufficiency
In a study conducted in patients with liver cirrhosis, the pharmacokinetics of a single application of DUROGESIC 50 mcg / hour were evaluated. Although the tmax and t½ values were not altered, the mean plasma Cmax and AUC values in these patients increased by approximately 35% and 73%, respectively. Patients with hepatic insufficiency should be carefully observed for signs of fentanyl toxicity and the dose reduced if necessary (see section 4.4 "Special warnings and precautions for use").
Kidney failure
Data from a study with intravenously administered fentanyl in renal transplant patients suggest that fentanyl clearance may be reduced in this patient population. Patients with renal insufficiency administered DUROGESIC should be carefully observed for signs of fentanyl toxicity and the dose reduced if necessary (see section 4.4 "Special warnings and precautions for use").
05.3 Preclinical safety data
In vitro fentanyl has shown, like other opioid analgesics, mutagenic effects on cultured mammalian cells only at cytotoxic concentrations and in case of metabolic activation. On the other hand, no mutagenic effect was found in the trials in vivo on rodents and bacteria. In a two-year study conducted in rats, administration of fentanyl was not associated with an "increased incidence of tumors at subcutaneous doses up to 33 micrograms / kg / day in males or 100 micrograms / kg / day in females ( equal to 0.16 and 0.39 times the daily human exposure obtained on the basis of the comparison of the AUC0-24h after application of a patch of 100 mcg / hour).
Some tests on female rats showed both reduced fertility and episodes of embryonic mortality. These observations are related to the toxicity of the drug towards the mother and not to a direct effect on the developing embryo. No teratogenic effect was found.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
- Polyethylene terephthalate / ethyl-vinyl acetate film
- Polyacrylate adhesive
- Siliconized polyester film
- Ink (orange / red / green / blue / gray)
06.2 Incompatibility
In order not to interfere with the adhesive properties of DUROGESIC, do not use creams, oils, lotions or powders in the area of the skin where the patch is to be applied.
06.3 Period of validity
2 years
06.4 Special precautions for storage
This medicine does not require any special storage conditions. Store in the original sealed bag.
06.5 Nature of the immediate packaging and contents of the package
Each transdermal patch is individually packaged in sealed pouches made of a multilayer laminated sheet (an acrylonitrate film, polyethylene terephthalate (PET), aluminum foil and low density polyethylene, adhesive).
The bags are packaged in lithographed cardboard boxes (3 bags per box) containing the package leaflet.
Packaging:
DUROGESIC 12 mcg / hour transdermal patch - orange box containing 3 matrix transdermal patches
DUROGESIC 25 mcg / hour transdermal patch - pink box containing 3 transdermal matrix patches
DUROGESIC 50 mcg / hour transdermal patch - green box containing 3 transdermal matrix patches
DUROGESIC 75 mcg / hour transdermal patch - blue box containing 3 transdermal matrix patches
DUROGESIC 100 mcg / hour transdermal patch - gray box containing 3 matrix transdermal patches
06.6 Instructions for use and handling
Application of the transdermal patch:
See section 4.2 for the method of administration of the DUROGESIC patch. Patches should be visually inspected prior to use. Cut, split, or otherwise damaged patches should not be used.
After removing the patch, fold it in half so that the sticky part closes on itself.
Then return the patch to its original sachet and throw it away safely and out of the reach and sight of children.
Wash your hands after applying and removing the patch.
No safety and pharmacokinetic data are available for other application sites other than that indicated.
07.0 MARKETING AUTHORIZATION HOLDER
JANSSEN-CILAG SpA
Via M. Buonarroti, 23
20093 COLOGNO MONZESE (MI)
08.0 MARKETING AUTHORIZATION NUMBER
DUROGESIC 12 mcg / hour transdermal patch - 3 transdermal matrix patches No. AIC 029212091
DUROGESIC 25 mcg / hour transdermal patch - 3 transdermal matrix patches
n. AIC 029212053
DUROGESIC 50 mcg / hour transdermal patch - 3 transdermal matrix patches
n. AIC 029212065
DUROGESIC 75 mcg / hour transdermal patch - 3 transdermal matrix patches
n. AIC 029212077
DUROGESIC 100 mcg / hour transdermal patch - 3 transdermal matrix patches
n. AIC 029212089
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: March 2007
Renewal of the authorization:
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of April 16, 2013
