A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Buprenorphine Transdermal Patch: learn about side effects, dosage, special precautions, and more on MedlinePlus. Fentanyl Transdermal Patch: learn about side effects, dosage, special precautions, and more on MedlinePlus.
There were no reports of abstinence syndrome or opioid withdrawal during conversion from entry opioid to Butec see section 4. There are no data from the use of Butec in pregnant women. Studies in animals have shown reproductive toxicity see Section 5.
The potential risk for humans is unknown. Towards the end of pregnancy high doses of buprenorphine may induce respiratory depression in the neonate even after a short period of administration.
Prolonged use of buprenorphine during pregnancy can result in neonatal opioid withdrawal syndrome. Therefore Butec should not be used during pregnancy and in women of childbearing potential who are not using effective contraception. Buprenorphine is excreted in human milk. Studies in rats have shown that buprenorphine may inhibit lactation. Therefore the use of Butec during lactation should be avoided.
No human data on the effect of buprenorphine on fertility are available. In a fertility and early embryonic development study, no effects on reproductive parameters were observed in male or female rats see section 5. Butec has a major influence on the ability to drive and use machines. Even when used according to instructions, Butec may affect the patient's reactions to such an extent that road safety and the ability to operate machinery may be impaired.
This applies particularly in the beginning of treatment and in conjunction with other centrally acting substances including alcohol, tranquillisers, sedatives and hypnotics. An individual recommendation should be given by the physician. A general restriction is not necessary in cases where a stable dose is used.
Patients who are affected and experience side effects e. This medicine can impair cognitive function and can affect a patient's ability to drive safely.
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act When prescribing this medicine, patients should be told:. This defence applies when:. Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found here: Serious adverse reactions that may be associated with Butec therapy in clinical use are similar to those observed with other opioid analgesics, including respiratory depression especially when used with other CNS depressants and hypotension see section 4.
Ear and labyrinth disorders. Respiratory, thoracic and mediastinal disorders. Musculoskeletal and connective tissue disorders. Renal and urinary disorders. Reproductive system and breast disorders.
General disorders and administration site condition s. Drug withdrawal syndrome neonatal. Injury, poisoning and procedural complications. In such cases treatment with Butec should be terminated.
Buprenorphine has a low risk of physical dependence. After discontinuation of Butec , withdrawal symptoms are unlikely. This may be due to the very slow dissociation of buprenorphine from the opioid receptors and to the gradual decrease of buprenorphine plasma concentrations usually over a period of 30 hours after removal of the last patch. However, after long-term use of Butec , withdrawal symptoms similar to those occurring during opioid withdrawal, cannot be entirely excluded.
These symptoms include agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal disorders. Reporting suspected adverse reactions after authorisation of the medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: Symptoms similar to those of other centrally acting analgesics are to be expected.
These include respiratory depression, sedation, drowsiness, nausea, vomiting, cardiovascular collapse and marked miosis. Remove any patches from the patient's skin.
Establish and maintain a patent airway, assist or control respiration as indicated and maintain adequate body temperature and fluid balance. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.
Treatment with continuous intravenous naloxone should begin with the usual doses but high doses may be required. Buprenorphine is a partial agonist opioid, acting at the mu opioid receptor. It also has antagonistic activity at the kappa opioid receptor.
Efficacy has been demonstrated in seven pivotal phase III studies of up to 12 weeks duration in patients with non-malignant pain of various aetiologies. These included patients with moderate and severe OA and back pain. Butec demonstrated clinically significant reductions in pain scores approximately 3 points on the BS scale and significantly greater pain control compared with placebo.
Studies in non-pregnant and pregnant rats have shown that buprenorphine passes the blood-brain and placental barriers. Concentrations in the brain which contained only unchanged buprenorphine after parenteral administration were times higher than after oral administration. After intramuscular or oral administration buprenorphine apparently accumulates in the foetal gastrointestinal lumen — presumably due to biliary excretion, as enterohepatic circulation has not fully developed.
Each patch provides a steady delivery of buprenorphine for up to seven days. Steady state is achieved during the first application. Following Butec application, buprenorphine diffuses from the patch through the skin. A study of bioavailability, relative to intravenous administration, confirms that this amount is systemically absorbed. Buprenorphine concentrations remain relatively constant during the 7-day patch application. A study in healthy subjects demonstrated that the pharmacokinetic profile of buprenorphine delivered by Butec is similar when applied to upper outer arm, upper chest, upper back or the side of the chest midaxillary line, 5th intercostal space.
In a study of healthy subjects receiving Butec repeatedly to the same site, an almost doubled exposure was seen with a 14 day rest period. For this reason, rotation of application sites is recommended, and a new patch should not be applied to the same skin site for weeks.
Concentrations returned to normal within 5 hours after the heat was removed. For this reason, applying direct heat sources such as hot water bottles, heat pads or electric blankets directly to the patch is not recommended. A heating pad applied to a Butec site immediately after patch removal did not alter absorption from the skin depot. Studies of intravenous buprenorphine have shown a large volume of distribution, implying extensive distribution of buprenorphine.
In a study of intravenous buprenorphine in healthy subjects, the volume of distribution at steady state was l, reflecting the large volume of distribution and lipophilicity of the active substance. Following intravenous administration, buprenorphine and its metabolites are secreted into bile, and within several minutes, distributed into the cerebrospinal fluid.
Buprenorphine metabolism in the skin following Butec application is negligible. Following transdermal application, buprenorphine is eliminated via hepatic metabolism, with subsequent biliary excretion and renal excretion of soluble metabolites. Norbuprenorphine is glucuronidated before elimination.
Buprenorphine is also eliminated in the faeces. No effect on fertility or general reproductive performance was observed in rats treated with buprenorphine. In embryofoetal developmental toxicity studies conducted in rats and rabbits using buprenorphine, no embryofoetal toxicity effects were observed.
In a rat pre- and post-natal developmental toxicity study with buprenorphine there was pup mortality, decreased pup body weight and concomitant maternal reduced food consumption and clinical signs. In long-term studies in rats and mice there was no evidence of any carcinogenic potential relevant for humans. In single- and repeat dose toxicity studies in rats, rabbits, guinea pigs, dogs and minipigs, Butec caused minimal or no adverse systemic events, whereas skin irritation was observed in all species examined.
Toxicological data available did not indicate a sensitising potential of the additives of the transdermal patches. Poly[acrylic acid-co-butylacrylate-co- 2-ethylhexyl acrylate-co-vinylacetate] 5: Separating foil between the adhesive matrices with and without buprenorphine: Poly Ethyleneterephthalate — foil.
Release liner on the front covering the adhesive matrix containing buprenorphine to be removed before applying the patch:. Sealed child resistant sachet, composed of identical top and bottom layers of heat-sealable laminate, comprising from outside to inside paper, PET, polyethylene-based copolymer, aluminium and poly acrylic acid-co-ethylene. When changing the patch, the used patch should be removed, the adhesive layer folded inwards on itself, and the patch disposed of safely and out of sight and reach of children.
Date of revision of the text. This information is intended for use by health professionals. For the full list of excipients, see section 6. Treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining adequate analgesia Butec is not suitable for the treatment of acute pain. Butec is indicated in adults.
Posology Butec should be administered every 7th day. Patients aged 18 years and over: No dosage adjustment of Butec is required in elderly patients.
Method of administration Route of administration: Patients with fever or exposed to external heat: Butec is contra-indicated in: Buprenorphine may lower the seizure threshold in patients with a history of seizure disorder. Because fentanyl is metabolised to inactive metabolites in the liver, hepatic impairment might delay its elimination.
If patients with hepatic impairment receive Fencino, they should be observed carefully for signs of fentanyl toxicity and the dose of Fencino reduced if necessary see section 5.
Even though impairment of renal function is not expected to affect fentanyl elimination to a clinically relevant extent, caution is advised because fentanyl pharmacokinetics has not been evaluated in this patient population see section 5.
If patients with renal impairment receive Fencino, they should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary. Fentanyl concentrations may increase if the skin temperature increases see section 5. Therefore, patients with fever should be monitored for opioid undesirable effects and the Fencino 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. All patients should be advised to avoid exposing the Fencino application site to direct external heat sources such as heating pads, electric blankets, heated water beds, heat or tanning lamps, sunbathing, hot water bottles, prolonged hot baths, saunas and hot whirlpool spa baths.
Caution is advised when Fencino is co-administered with medicinal products that affect the serotonergic neurotransmitter systems. This may occur within the recommended dose. The concomitant use of Fencino with cytochrome P 3A4 CYP3A4 inhibitors 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. Therefore, the concomitant use of Fencino and CYP3A4 inhibitors is not recommended unless the benefits outweigh the increased risk of adverse effects.
Generally, a patient should wait for 2 days after stopping treatment with a CYP3A4 inhibitor before applying the first Fencino patch. However, the duration of inhibition varies and for some CYP3A4 inhibitors with a long elimination half-life, such as amiodarone, or for time-dependent inhibitors such as erythromycin, idelalisib, nicardipine and ritonavir, this period may need to be longer.
Therefore, the product information of the CYP3A4 inhibitor must be consulted for the active substance's half-life and duration of the inhibitory effect before applying the first Fencino patch. A patient who is treated with Fencino should wait at least 1 week after removal of the last patch before initiating treatment with a CYP3A4 inhibitor. If concomitant use of Fencino with a CYP3A4 inhibitor cannot be avoided, close monitoring for signs or symptoms of increased or prolonged therapeutic effects and adverse effects of fentanyl in particular respiratory depression is warranted, and the Fencino dosage must be reduced or interrupted as deemed necessary see section 4.
Accidental transfer of a fentanyl patch to the skin of a non-patch wearer particularly a child , while sharing a bed or being in close physical contact with a patch wearer, may result in an opioid overdose for the non-patch wearer. Patients should be advised that if accidental patch transfer occurs, the transferred patch must be removed immediately from the skin of the non-patch wearer see section 4. 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 active substance than younger patients.
If elderly patients receive Fencino, they should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary see section 5. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract.
The resultant prolongation in gastrointestinal transit time may be responsible for the constipating effect of fentanyl.
Patients should be advised on measures to prevent constipation and prophylactic laxative use should be considered. Extra caution should be used in patients with chronic constipation. If paralytic ileus is present or suspected, treatment with Fencino should be stopped. Non-epileptic myo clonic reactions can occur.
Caution should be exercised when treating patients with myasthenia gravis. The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended see also section 4. The potential for serious or life-threatening hypoventilation exists regardless of the dose of Fencino transdermal system administered. Fencino has not been studied in children under 2 years of age. Fencino should be administered only to opioid-tolerant children age 2 years or older see section 4.
To guard against accidental ingestion by children, use caution when choosing the application site for Fencino see sections 4. The concomitant use of other central nervous system depressants, including opioids, sedatives, hypnotics, general anaesthetics, phenothiazines, tranquilizers, sedating antihistamines, and alcoholic beverages and skeletal muscle relaxants, may produce additive depressant effects; hypoventilation, hypotension, profound sedation, coma or death may occur.
Therefore, the use of any of these medicinal products concomitantly with Fencino requires special patient care and observation. Fencino is not recommended for use in patients who require the concomitant administration of an MAOI.
Severe and unpredictable interactions with MAOIs, involving the potentiation of opiate effects or the potentiation of serotoninergic effects, have been reported. The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect.
The dose and duration of concomitant use should be limited see section 4. 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. Fentanyl, a high clearance active substance, is rapidly and extensively metabolised mainly by CYP3A4.
Cases of serious respiratory depression after coadministration of CYP3A4 inhibitors with transdermal fentanyl have been reported, including a fatal case after coadministration with a moderate CYP3A4 inhibitor. The concomitant use of CYP3A4 inhibitors and Fencino is not recommended, unless the patient is closely monitored see section 4.
Examples of active substances that may increase fentanyl concentrations include: The extent of the interactions of CYP3A4 inhibitors with long-term transdermal fentanyl administration is not known, but may be greater than with short-term intravenous administration. The concomitant use of transdermal fentanyl with CYP3A4 inducers may result in a decrease in fentanyl plasma concentrations and a decreased therapeutic effect.
The dose of Fencino may need to be increased or a switch to another analgesic active substance may be needed. A fentanyl dose decrease and careful monitoring is warranted in anticipation of stopping concomitant treatment with a CYP3A4 inducer. The effects of the inducer decline gradually and may result in increased fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression.
Careful monitoring should be continued until stable drug effects are achieved. Examples of active substances that may decrease fentanyl plasma concentrations include: There are no adequate data from the use of fentanyl in pregnant women. Studies in animals have shown some reproductive toxicity see section 5. The potential risk for humans is unknown, although fentanyl as an IV anaesthetic has been found to cross the placenta in human pregnancies.
Neonatal withdrawal syndrome has been reported in newborn infants with chronic maternal use of transdermal fentanyl during pregnancy. Fencino should not be used during pregnancy unless clearly necessary. Use of Fencino during childbirth is not recommended because it should not be used in the management of acute or postoperative pain see section 4. Moreover, because fentanyl passes through the placenta, the use of Fencino during childbirth might result in respiratory depression in the newborn infant.
Breastfeeding should therefore be discontinued during treatment with Fencino and for at least 72 hours after removal of the patch. There are no clinical data on the effects of fentanyl on fertility. Some studies in rats have revealed reduced fertility and enhanced embryo mortality at maternally toxic doses see section 5. This medicine can impair cognitive function and can affect a patient's ability to drive safely.
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act When prescribing this medicine, patients should be told:. The safety of fentanyl patches was evaluated in adult and paediatric subjects who participated in 11 clinical studies 1 double-blind, placebo-controlled; 7 open-label, active-controlled; 3 open-label, uncontrolled used for the management of chronic malignant or non-malignant pain.
These subjects received at least one dose of fentanyl and provided safety data. The adverse reactions reported with the use of fentanyl patches from these clinical studies, including the above-mentioned adverse reactions, and from post-marketing experiences are listed below in Table 5. The displayed frequency categories use the following convention: The adverse reactions are presented by System Organ Class and in order of decreasing seriousness within each frequency category.
Adverse reactions in adult and paediatric patients. Anaphylactic shock, Anaphylactic reaction, Anaphylactoid reaction. Insomnia, Depression, Anxiety, Confusional state, Hallucination. Hypoaesthesia, Convulsion including clonic convulsions and grand mal convulsion , Amnesia, Depressed level of consciousness, Loss of consciousness.
Ear and labyrinth disorders. Respiratory, thoracic and mediastinal disorders. Skin and subcutaneous tissue disorders. Hyperhidrosis, Pruritus, Rash, Erythema. Musculoskeletal and connective tissue disorders. Renal and urinary disorders. Reproductive system and breast disorders. Erectile dysfunction, Sexual dysfunction. General disorders and administration site conditions.
Fatigue, Oedema peripheral, Asthenia, Malaise, Feeling cold. These subjects received at least one dose of fentanyl and provided safety data see section 5. The safety profile in children and adolescents treated with fentanyl patches was similar to that observed in adults. No risk was identified in the paediatric population beyond that expected with the use of opioids for the relief of pain associated with serious illness and there does not appear to be any paediatric-specific risk associated with fentanyl patch use in children as young as 2 years old when used as directed.
Based on pooled safety data from these 3 clinical studies in paediatric subjects, the most commonly reported i. Tolerance, physical dependence, and psychological dependence can develop on repeated use of Fencino see section 4.
Opioid withdrawal symptoms such as nausea, vomiting, diarrhoea, anxiety and shivering are possible in some patients after conversion from their previous opioid analgesic to Fencino or if therapy is stopped suddenly see section 4.
There have been very rare reports of newborn infants experiencing neonatal withdrawal syndrome when mothers chronically used Fencino during pregnancy see section 4. Cases of serotonin syndrome have been reported when fentanyl was administered concomitantly with highly serotonergic drugs see sections 4.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card scheme at www. The manifestations of fentanyl overdose are an extension of its pharmacologic actions, the most serious effect being respiratory depression.
For management of respiratory depression, immediate countermeasures include removing the Fencino patch 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.
If severe or persistent hypotension occurs, hypovolemia should be considered, and the condition should be managed with appropriate parenteral fluid therapy. Its primary therapeutic actions are analgesia and sedation. The safety of fentanyl patches was evaluated in 3 open-label studies in paediatric subjects with chronic pain, aged 2 to 17 years, inclusive. Eighty of the children were aged 2 to 6 years, inclusive. Of these subjects, 23 Fencino provides continuous systemic delivery of fentanyl during the hour application period.
Following Fencino application, the skin under the system absorbs fentanyl, and a depot of fentanyl concentrates in the upper skin layers. Fentanyl then becomes available to the systemic circulation. The polymer matrix and the diffusion of fentanyl through the layers of the skin ensure that the release rate is relatively constant. The concentration gradient existing between the system and the lower concentration in the skin drives drug release.
After the first patch application, serum fentanyl concentrations increase gradually, generally leveling off between 12 and 24 hours and remaining relatively constant for the remainder of the hour application period.
By the end of the second hour application, a steady-state serum concentration is reached and is maintained during subsequent applications of a patch of the same size. Patients reach and maintain a steady-state serum concentration that is determined by individual variation in skin permeability and body clearance of fentanyl.
High inter-subject variability in plasma concentrations has been observed. Skin temperature elevation may enhance the absorption of transdermally-applied fentanyl see section 4. An increase in skin temperature through the application of a heating pad on low setting over the Fencino system during the first 10 hours of a single application increased the mean fentanyl AUC value by 2.
Fentanyl accumulates in skeletal muscle and fat and is released slowly into blood. Fentanyl crosses the blood-brain barrier easily. It also crosses the placenta and is excreted in breast milk. Fentanyl is a high clearance active substance and is rapidly and extensively metabolised primarily by CYP3A4 in the liver. The major metabolite, norfentanyl, and other metabolites are inactive.
Skin does not appear to metabolise fentanyl delivered transdermally. Following a hour patch application, the mean fentanyl half-life ranges from 20 to 27 hours. As a result of continued absorption of fentanyl from the skin depot after removal of the patch, the half-life of fentanyl after transdermal administration is about 2- to 3-fold longer than intravenous administration. The serum fentanyl concentrations attained are proportional to the patch size. The pharmacokinetics of transdermal fentanyl do not change with repeated application.
There is a high inter-subject variability in fentanyl pharmacokinetics, in the relationships between fentanyl concentrations, therapeutic and adverse effects, and in opioid tolerance. The minimum effective fentanyl concentration depends on the pain intensity and the previous use of opioid therapy. Both the minimum effective concentration and the toxic concentration increase with tolerance. An optimal therapeutic concentration range of fentanyl can therefore not be established.
Adjustment of the individual fentanyl dose must be based on the patient's response and level of tolerance. A lag time of 12 to 24 hours after application of the first patch and after a dose increase must be taken into account. 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.
In a study conducted with fentanyl transdermal patches, healthy elderly subjects had fentanyl pharmacokinetics which did not differ significantly from healthy young subjects although peak serum concentrations tended to be lower and mean half-life values were prolonged to approximately 34 hours.
Elderly patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary see section 4. However, as the influence of renal impairment on the pharmacokinetics of fentanyl has not been evaluated, caution is advised see sections 4.
Patients with hepatic impairment should be observed carefully for signs of fentanyl toxicity and the dose of Fencino should be reduced if necessary see section 4. Data in subjects with cirrhosis and simulated data in subjects with different grades of impaired liver function treated with transdermal fentanyl suggest that fentanyl concentrations may be increased, and fentanyl clearance may be decreased compared to subjects with normal liver function.
Fentanyl concentrations were measured in more than children aged 2 to 17 years who were applied fentanyl patches in the dose range of These findings have been taken into consideration in determining the dosing recommendations for paediatric patients see sections 4. Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity. Standard reproductive and developmental toxicity studies have been carried out using parenteral administration of fentanyl.
In a rat study fentanyl did not influence male fertility. Some studies with female rats revealed reduced fertility and enhanced embryo mortality. Effects on the embryo were due to maternal toxicity and not to direct effects of the substance on the developing embryo.
There was no indication of teratogenic effects in studies in two species rats and rabbits. In a study on pre- and postnatal development the survival rate of offspring was significantly reduced at doses which slightly reduced maternal weight. This effect could either be due to altered maternal care or a direct effect of fentanyl on the pups.
Effects on somatic development and behaviour of the offspring were not observed. Mutagenicity testing in bacteria and in rodents yielded negative results. Fentanyl induced mutagenic effects in mammalian cells in vitro , comparable to other opioid analgesics. A mutagenic risk for the use of therapeutic doses seems unlikely since effects appeared only at high concentrations.
A carcinogenicity study daily subcutaneous injections of fentanyl hydrochloride for two years in Sprague Dawley rats did not induce any findings indicative of oncogenic potential.
To prevent interference with the adhesive properties of the patch, no creams, oils, lotions or powder should be applied to the skin area when the patch is applied. Each transdermal patch is packed individually into a sealed child resistant sachet.
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Fentanyl Transdermal Patch
Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in. A transdermal patch is a patch that attaches to your skin and contains medication. The drug from the patch is absorbed into your body over a. There are various types of transdermal technology, including patches and microneedles. Learn all about transdermal drugs and how they permeates the skin.