When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Each Durogesic DTrans patch is marked:
Durogesic
12, 25, 50, 75 or 100 µg fentanyl/h
Durogesic DTrans is a sustained-release preparation indicated for the treatment of chronic intractable pain in patients requiring opioid analgesia and is contraindicated in acute or postoperative pain because of the lack of opportunity for dosage titration in the short term and the resultant possibility of serious or life threatening respiratory depression. Change to section 4.4- DUROGESIC SHOULD NOT BE USED IN THE MANAGEMENT OF ACUTE OR POSTOPERATIVE PAIN SINCE THERE IS NO OPPORTUNITY FOR DOSE TITRATION DURING SHORT-TERM USE AND BECAUSE SERIOUS OR LIFE‑THREATENING HYPOVENTILATION COULD RESULT. PATIENTS WHO HAVE EXPERIENCED SERIOUS ADVERSE EVENTS SHOULD BE MONITORED FOR UP TO 24 HOURS AFTER DUROGESIC REMOVAL SINCE SERUM FENTANYL CONCENTRATIONS DECLINE GRADUALLY AND ARE REDUCED BY ABOUT 50% 17 (RANGE 13-22) HOURS LATER (see Section 5.2, Pharmacokinetic Properties) Patients who have experienced serious adverse events should be monitored for up to 24 hours after Durogesic DTrans removal since serum fentanyl concentrations decline gradually with mean half-life ranging from 20-27 hours. Do not cut Durogesic DTrans patches should not be cut.. A patch that has been divided, cut or damaged in any way should not be used. Drug dependence and potential for abuse Tolerance, physical dependence and psychological dependence may develop upon repeated administration of opioids. Iatrogenic addiction following opioid administration is rare. Patients with a prior history of drug dependence/alcohol abuse are more at risk to develop dependence and abuse in opioid treatment. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse or addiction. Fentanyl can be abused in a manner similar to other opioid agonists. Abuse or intentional misuse of Durogesic DTrans may result in overdose and/or death. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations, however, these patients will require intensive monitoring for signs of misuse, abuse or addiction. Opioids may cause hypotension, especially in patients with acute hypovolaemia. Underlying, symptomatic hypotension and/or hypovolaemia should be corrected before treatment with fentanyl transdermal patches is initiated Patients with fever/external heat A pharmacokinetic model suggests that serum fentanyl concentrations may increase by about one-third if the skin temperature increases to 40° C. Therefore, patients with fever should be monitored for opioid side effects and the Durogesic DTrans dose should be adjusted if necessary. There is a potential for temperature-dependent increases in fentanyl released from the system resulting in possible overdose and death. A clinical pharmacology trial conducted in healthy adult subjects has shown that the application of heat over the Durogesic DTrans transdermal system increased mean fentanyl AUC values by 120% and mean Cmax values by 61%. Patients who develop fever should be monitored for opioid side effects since significant increases in body temperature can potentially increase fentanyl delivery rate. Interactions with other Medicinal Products: Interactions with CYP3A4 inhibitors The concomitant use of Durogesic DTrans with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation special patient care and observation are appropriate. Therefore, the concomitant use of transdermal fentanyl and CYP3A4 inhibitors is not recommended unless the patient is closely monitored. Patients, especially those who are receiving Durogesic DTrans and CYP3A4 inhibitors, should be monitored for signs of respiratory depression and dosage adjustments should be made if warranted. Concomitant use of mixed agonists/antagonists The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended (see also Section 4.5). Use in Elderly Patients Data from intravenous studies with fentanyl suggest that elderly patients may have reduced clearance, a prolonged half-life, and they may be more sensitive to the drug than younger patients. If elderly patients receive Durogesic, they should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary (see Section 5.2, Pharmacokinetic properties). Lactation As fentanyl is excreted into breast milk, breastfeeding should be discontinued during treatment with Durogesic (see also Section 4.6). Patients with myasthenia gravis Non-epileptic (myo)clonic reactions can occur. Caution should be exercised when treating patients with myasthenia gravis. Change to section 4.5- The concomitant use of other CNS depressants, including opioids, sedatives, anxiolytics, hypnotics, general anaesthetics, phenothiazines, tranquilisers, antipsychotics, skeletal muscle relaxants, sedating antihistamines and alcoholic beverages may produce additive depressant effects; hypoventilation, hypotension and profound sedation, coma or death may occur. Therefore, the use of any of these drugs concomitantly with Durogesic DTrans requires special care and observation. Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of IV fentanyl. Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds. The concomitant use of transdermal fentanyl with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation, special patient care and observation are appropriate. The concomitant use of CYP3A4 inhibitors and transdermal fentanyl is not recommended, unless the patient is closely monitored for an extended period of time and dosage adjustments made if warranted (See also 4.4 Special Warnings and Precautions for Use). Concomitant use of mixed agonists/antagonists The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients (see also Section 4.4). Change to section 4.6- There are no adequate data from the use of Durogesic in pregnant women. Studies in animals have shown some reproductive toxicity (see Section 5.3, preclinical safety data). The potential risk for humans is unknown, although fentanyl as an IV anesthetic has been found to cross the placenta in early human pregnancies. . Neonatal withdrawal syndrome has been reported in newborn infants with chronic maternal use of Durogesic DTrans during pregnancy. Durogesic DTrans should not be used during pregnancy unless clearly necessary. Use of Durogesic DTrans during childbirth is not recommended because it should not be used in the management of acute or postoperative pain (see section 4.3 Contraindications and 4.4, Special Warning and Precautions). Change to section 4.7-Durogesic DTrans may impair the mental and/or physical ability required to perform potentially hazardous tasks such as driving a car or operating machinery. Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
DUROGESIC SHOULD NOT BE USED IN THE MANAGEMENT OF ACUTE OR POSTOPERATIVE PAIN SINCE THERE IS NO OPPORTUNITY FOR DOSE TITRATION DURING SHORT-TERM USE AND BECAUSE SERIOUS OR LIFE‑THREATENING HYPOVENTILATION COULD RESULT.
PATIENTS WHO HAVE EXPERIENCED SERIOUS ADVERSE EVENTS SHOULD BE MONITORED FOR UP TO 24 HOURS AFTER DUROGESIC REMOVAL SINCE SERUM FENTANYL CONCENTRATIONS DECLINE GRADUALLY AND ARE REDUCED BY ABOUT 50% 17 (RANGE 13-22) HOURS LATER (see Section 5.2, Pharmacokinetic Properties)
Patients who have experienced serious adverse events should be monitored for up to 24 hours after Durogesic DTrans removal since serum fentanyl concentrations decline gradually with mean half-life ranging from 20-27 hours.
Do not cut Durogesic DTrans patches should not be cut.. A patch that has been divided, cut or damaged in any way should not be used. Drug dependence and potential for abuse Tolerance, physical dependence and psychological dependence may develop upon repeated administration of opioids. Iatrogenic addiction following opioid administration is rare. Patients with a prior history of drug dependence/alcohol abuse are more at risk to develop dependence and abuse in opioid treatment. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse or addiction. Fentanyl can be abused in a manner similar to other opioid agonists. Abuse or intentional misuse of Durogesic DTrans may result in overdose and/or death. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations, however, these patients will require intensive monitoring for signs of misuse, abuse or addiction. Opioids may cause hypotension, especially in patients with acute hypovolaemia. Underlying, symptomatic hypotension and/or hypovolaemia should be corrected before treatment with fentanyl transdermal patches is initiated Patients with fever/external heat A pharmacokinetic model suggests that serum fentanyl concentrations may increase by about one-third if the skin temperature increases to 40° C. Therefore, patients with fever should be monitored for opioid side effects and the Durogesic DTrans dose should be adjusted if necessary. There is a potential for temperature-dependent increases in fentanyl released from the system resulting in possible overdose and death. A clinical pharmacology trial conducted in healthy adult subjects has shown that the application of heat over the Durogesic DTrans transdermal system increased mean fentanyl AUC values by 120% and mean Cmax values by 61%. Patients who develop fever should be monitored for opioid side effects since significant increases in body temperature can potentially increase fentanyl delivery rate. Interactions with other Medicinal Products: Interactions with CYP3A4 inhibitors The concomitant use of Durogesic DTrans with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation special patient care and observation are appropriate. Therefore, the concomitant use of transdermal fentanyl and CYP3A4 inhibitors is not recommended unless the patient is closely monitored. Patients, especially those who are receiving Durogesic DTrans and CYP3A4 inhibitors, should be monitored for signs of respiratory depression and dosage adjustments should be made if warranted. Concomitant use of mixed agonists/antagonists The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended (see also Section 4.5). Use in Elderly Patients Data from intravenous studies with fentanyl suggest that elderly patients may have reduced clearance, a prolonged half-life, and they may be more sensitive to the drug than younger patients. If elderly patients receive Durogesic, they should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary (see Section 5.2, Pharmacokinetic properties). Lactation As fentanyl is excreted into breast milk, breastfeeding should be discontinued during treatment with Durogesic (see also Section 4.6). Patients with myasthenia gravis Non-epileptic (myo)clonic reactions can occur. Caution should be exercised when treating patients with myasthenia gravis. Change to section 4.5- The concomitant use of other CNS depressants, including opioids, sedatives, anxiolytics, hypnotics, general anaesthetics, phenothiazines, tranquilisers, antipsychotics, skeletal muscle relaxants, sedating antihistamines and alcoholic beverages may produce additive depressant effects; hypoventilation, hypotension and profound sedation, coma or death may occur. Therefore, the use of any of these drugs concomitantly with Durogesic DTrans requires special care and observation. Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of IV fentanyl. Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds. The concomitant use of transdermal fentanyl with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation, special patient care and observation are appropriate. The concomitant use of CYP3A4 inhibitors and transdermal fentanyl is not recommended, unless the patient is closely monitored for an extended period of time and dosage adjustments made if warranted (See also 4.4 Special Warnings and Precautions for Use). Concomitant use of mixed agonists/antagonists The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients (see also Section 4.4). Change to section 4.6- There are no adequate data from the use of Durogesic in pregnant women. Studies in animals have shown some reproductive toxicity (see Section 5.3, preclinical safety data). The potential risk for humans is unknown, although fentanyl as an IV anesthetic has been found to cross the placenta in early human pregnancies. . Neonatal withdrawal syndrome has been reported in newborn infants with chronic maternal use of Durogesic DTrans during pregnancy. Durogesic DTrans should not be used during pregnancy unless clearly necessary. Use of Durogesic DTrans during childbirth is not recommended because it should not be used in the management of acute or postoperative pain (see section 4.3 Contraindications and 4.4, Special Warning and Precautions). Change to section 4.7-Durogesic DTrans may impair the mental and/or physical ability required to perform potentially hazardous tasks such as driving a car or operating machinery. Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Do not cut Durogesic DTrans patches should not be cut.. A patch that has been divided, cut or damaged in any way should not be used.
Drug dependence and potential for abuse
Tolerance, physical dependence and psychological dependence may develop upon repeated administration of opioids. Iatrogenic addiction following opioid administration is rare. Patients with a prior history of drug dependence/alcohol abuse are more at risk to develop dependence and abuse in opioid treatment. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse or addiction. Fentanyl can be abused in a manner similar to other opioid agonists. Abuse or intentional misuse of Durogesic DTrans may result in overdose and/or death. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations, however, these patients will require intensive monitoring for signs of misuse, abuse or addiction.
Opioids may cause hypotension, especially in patients with acute hypovolaemia. Underlying, symptomatic hypotension and/or hypovolaemia should be corrected before treatment with fentanyl transdermal patches is initiated
Patients with fever/external heat
A pharmacokinetic model suggests that serum fentanyl concentrations may increase by about one-third if the skin temperature increases to 40° C. Therefore, patients with fever should be monitored for opioid side effects and the Durogesic DTrans dose should be adjusted if necessary. There is a potential for temperature-dependent increases in fentanyl released from the system resulting in possible overdose and death. A clinical pharmacology trial conducted in healthy adult subjects has shown that the application of heat over the Durogesic DTrans transdermal system increased mean fentanyl AUC values by 120% and mean Cmax values by 61%.
Patients who develop fever should be monitored for opioid side effects since significant increases in body temperature can potentially increase fentanyl delivery rate.
Interactions with other Medicinal Products:
Interactions with CYP3A4 inhibitors
The concomitant use of Durogesic DTrans with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation special patient care and observation are appropriate. Therefore, the concomitant use of transdermal fentanyl and CYP3A4 inhibitors is not recommended unless the patient is closely monitored. Patients, especially those who are receiving Durogesic DTrans and CYP3A4 inhibitors, should be monitored for signs of respiratory depression and dosage adjustments should be made if warranted.
Concomitant use of mixed agonists/antagonists
The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended (see also Section 4.5).
Use in Elderly Patients
Data from intravenous studies with fentanyl suggest that elderly patients may have reduced clearance, a prolonged half-life, and they may be more sensitive to the drug than younger patients. If elderly patients receive Durogesic, they should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary (see Section 5.2, Pharmacokinetic properties).
Lactation
As fentanyl is excreted into breast milk, breastfeeding should be discontinued during treatment with Durogesic (see also Section 4.6).
Patients with myasthenia gravis
Non-epileptic (myo)clonic reactions can occur. Caution should be exercised when treating patients with myasthenia gravis. Change to section 4.5- The concomitant use of other CNS depressants, including opioids, sedatives, anxiolytics, hypnotics, general anaesthetics, phenothiazines, tranquilisers, antipsychotics, skeletal muscle relaxants, sedating antihistamines and alcoholic beverages may produce additive depressant effects; hypoventilation, hypotension and profound sedation, coma or death may occur. Therefore, the use of any of these drugs concomitantly with Durogesic DTrans requires special care and observation. Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of IV fentanyl. Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds. The concomitant use of transdermal fentanyl with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation, special patient care and observation are appropriate. The concomitant use of CYP3A4 inhibitors and transdermal fentanyl is not recommended, unless the patient is closely monitored for an extended period of time and dosage adjustments made if warranted (See also 4.4 Special Warnings and Precautions for Use). Concomitant use of mixed agonists/antagonists The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients (see also Section 4.4). Change to section 4.6- There are no adequate data from the use of Durogesic in pregnant women. Studies in animals have shown some reproductive toxicity (see Section 5.3, preclinical safety data). The potential risk for humans is unknown, although fentanyl as an IV anesthetic has been found to cross the placenta in early human pregnancies. . Neonatal withdrawal syndrome has been reported in newborn infants with chronic maternal use of Durogesic DTrans during pregnancy. Durogesic DTrans should not be used during pregnancy unless clearly necessary. Use of Durogesic DTrans during childbirth is not recommended because it should not be used in the management of acute or postoperative pain (see section 4.3 Contraindications and 4.4, Special Warning and Precautions). Change to section 4.7-Durogesic DTrans may impair the mental and/or physical ability required to perform potentially hazardous tasks such as driving a car or operating machinery. Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of IV fentanyl. Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds.
The concomitant use of transdermal fentanyl with cytochrome P450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation, special patient care and observation are appropriate. The concomitant use of CYP3A4 inhibitors and transdermal fentanyl is not recommended, unless the patient is closely monitored for an extended period of time and dosage adjustments made if warranted (See also 4.4 Special Warnings and Precautions for Use). Concomitant use of mixed agonists/antagonists The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients (see also Section 4.4). Change to section 4.6- There are no adequate data from the use of Durogesic in pregnant women. Studies in animals have shown some reproductive toxicity (see Section 5.3, preclinical safety data). The potential risk for humans is unknown, although fentanyl as an IV anesthetic has been found to cross the placenta in early human pregnancies. . Neonatal withdrawal syndrome has been reported in newborn infants with chronic maternal use of Durogesic DTrans during pregnancy. Durogesic DTrans should not be used during pregnancy unless clearly necessary. Use of Durogesic DTrans during childbirth is not recommended because it should not be used in the management of acute or postoperative pain (see section 4.3 Contraindications and 4.4, Special Warning and Precautions). Change to section 4.7-Durogesic DTrans may impair the mental and/or physical ability required to perform potentially hazardous tasks such as driving a car or operating machinery. Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients (see also Section 4.4). Change to section 4.6- There are no adequate data from the use of Durogesic in pregnant women. Studies in animals have shown some reproductive toxicity (see Section 5.3, preclinical safety data). The potential risk for humans is unknown, although fentanyl as an IV anesthetic has been found to cross the placenta in early human pregnancies. . Neonatal withdrawal syndrome has been reported in newborn infants with chronic maternal use of Durogesic DTrans during pregnancy. Durogesic DTrans should not be used during pregnancy unless clearly necessary. Use of Durogesic DTrans during childbirth is not recommended because it should not be used in the management of acute or postoperative pain (see section 4.3 Contraindications and 4.4, Special Warning and Precautions). Change to section 4.7-Durogesic DTrans may impair the mental and/or physical ability required to perform potentially hazardous tasks such as driving a car or operating machinery. Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Use of Durogesic DTrans during childbirth is not recommended because it should not be used in the management of acute or postoperative pain (see section 4.3 Contraindications and 4.4, Special Warning and Precautions). Change to section 4.7-Durogesic DTrans may impair the mental and/or physical ability required to perform potentially hazardous tasks such as driving a car or operating machinery. Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Change to section 4.8-Addition of paediatric wording and updated paediatric table Change to section 4.9- Symptoms: The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression. Treatment: For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines. If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Symptoms:
The manifestations of fentanyl overdosage are an extension of its pharmacological actions, the most serious effect being respiratory depression.
Treatment:
For management of respiratory depression, immediate countermeasures include removing Durogesic DTrans and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone. Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines.
If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained Change to section 5.2- Elimination After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Elimination
After Durogesic DTrans is removed, serum fentanyl concentrations decline gradually, falling about 50% in about 17 (range 13-22) hours following a 24-hour application. Following a 72-hour application, the mean half-life ranges from 20-27 hours.
Therefore, Durogesic DTrans should not be used within 14 days after discontinuation of treatment with MAOIs.
Change to section 10 - Date of revision of the text
June 2010
Change to section 4.8 - Undesirable effects
Updated into MedRA format.
Change to section 7 – Marketing Authorisation Holder
Change of address
Change to section 10 – Date of revision of text
August 2008
Change to section 4.2 – Posology and Method of Administration
Information added regarding application and removal of patches.
Change to section 4.4 – Special Warnings and Precautions for Use
Information added to sections “Drug dependence and potential for abuse” and “Patients with fever/external heat”.
Change to section 4.6 – Pregnancy and Lactation
Information added regarding use in pregnancy, childbirth and breast feeding.
Change to section 4.8 – Undesirable effects
Information added regarding neonatal withdrawal syndrome.
Change to section 5.3 - Preclinical Safety Data
Information added regarding in vitro and in vivo studies.
July 2008
Change to section 9 – Date of Renewal of Authorisation
Change to section 4.2 – Posology and |Method of Administration
Addition of paediatric Posology
Addition of paediatric information. Wording included on accidental ingestion.
Addition of AEs in children and adolescents
Change to section 5.1 - Pharmacodynamic properties
Addition of Clinical Trial data on paediatric patients
Change to section 5.2 - Pharmacokinetic properties
Addition of paediatric PK information
Change to section 6.6 – Instructions for use, handling and disposal
Addition of wording informing there is no safety and PK data available for other application sites.
Further details added for application site, use in opioid tolerant patients, use in opioid-naive patients, withdrawal symptoms.
Change to section 4.3 – Contra-indications
- Change in wording regarding respiratory depression.
- Addition of paragraph for "Opioid-naïve and not opioid-tolerant states"
- Addition of text regarding potential for abuse, misuse or addiction of product
- Addition of paragraph regarding "Interactions with CYP3A4 Inhibitors"
Change to section 4.5 –Interaction with other medicinal products and other forms of interaction
- Further details added for concomitant use with CNS depressants, potent CYP3A4 inhibitors.
- Addition of paragraph regarding "Monoamine Oxidase Inhibitors
- Information added for Clinical Trials and Postmarketing Experience.
May 2007
4.4
Special Warnings and Precautions for Use
Text added advising that patients should not be changed from one brand of fentanyl transdermal patches to another without specific counselling on the change from their healthcare professionals.
10.
DATE OF REVISION OF THE TEXT
November 2006
1.
Addition of 12 microgram/hour information to the SmPC
2.
4.2
Posology and method of administration
5.2
Pharmacokinetic properties
6.1
List of excipients
8.
MARKETING AUTHORISATION NUMBER(S)
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
September 2006