Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fentanyl, quantity: 16.8 mg - drug delivery system, transdermal - excipient ingredients: polyethylene terephthalate; ethyl acetate; 2-ethylhexyl acrylate; vinyl acetate; 2,2'-azobisisobutyronitrile; 2-hydroxyethyl acrylate - for the management of pain associated with cancer, palliative cancer and other conditions in patients where: - other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and - the pain is opioid-responsive, and - severe enough to require daily, continuous long term opioid treatment. not for use in opioid-naive patients.

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fentanyl, quantity: 2.1 mg - drug delivery system, transdermal - excipient ingredients: polyethylene terephthalate; ethyl acetate; 2-ethylhexyl acrylate; vinyl acetate; 2,2'-azobisisobutyronitrile; 2-hydroxyethyl acrylate - for the management of pain associated with cancer, palliative cancer and other conditions in patients where: - other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and - the pain is opioid-responsive, and - severe enough to require daily, continuous long term opioid treatment. not for use in opioid-naive patients.

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fentanyl, quantity: 8.4 mg - drug delivery system, transdermal - excipient ingredients: polyethylene terephthalate; ethyl acetate; 2-ethylhexyl acrylate; vinyl acetate; 2,2'-azobisisobutyronitrile; 2-hydroxyethyl acrylate - for the management of pain associated with cancer, palliative cancer and other conditions in patients where: - other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and - the pain is opioid-responsive, and - severe enough to require daily, continuous long term opioid treatment. not for use in opioid-naive patients.

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fentanyl, quantity: 4.2 mg - drug delivery system, transdermal - excipient ingredients: polyethylene terephthalate; ethyl acetate; 2-ethylhexyl acrylate; vinyl acetate; 2,2'-azobisisobutyronitrile; 2-hydroxyethyl acrylate - for the management of pain associated with cancer, palliative cancer and other conditions in patients where: - other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and - the pain is opioid-responsive, and - severe enough to require daily, continuous long term opioid treatment. not for use in opioid-naive patients.

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fentanyl, quantity: 12.6 mg - drug delivery system, transdermal - excipient ingredients: polyethylene terephthalate; ethyl acetate; 2-ethylhexyl acrylate; vinyl acetate; 2,2'-azobisisobutyronitrile; 2-hydroxyethyl acrylate - for the management of pain associated with cancer, palliative cancer and other conditions in patients where: - other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and - the pain is opioid-responsive, and - severe enough to require daily, continuous long term opioid treatment. not for use in opioid-naive patients.

United States - English - NLM (National Library of Medicine)

alvogen - fentanyl (unii: uf599785jz) (fentanyl - unii:uf599785jz) - fentanyl 12.5 ug - fentanyl transdermal system is indicated for the management of severe and persistent pain in opioid-tolerant patients, that requires an extended treatment period with a daily opioid analgesic in opioid-tolerant patients, and for which alternative treatment options are inadequate. patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration , and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions ( 5.1) ], reserve fentanyl transdermal system for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - fentanyl transdermal system is not indicated as an as-needed (prn) analgesic. fentanyl transdermal system is contraindicated in: - patients who are not opioid-tolerant. - the management of acute or intermittent pain, or in patients who require opioid analgesia for a short period of time. - the management of post-operative pain, including use after outpatient or day surgeries, (e.g., tonsillectomies). - the management of mild pain. - patients with significant respiratory depression [see warnings and precautions ( 5.12) ]. - patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions ( 5.12) ]. - patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.19) ]. - patients with hypersensitivity to fentanyl (e.g., anaphylaxis) or any components of the transdermal system [see adverse reactions ( 6.2) ]. risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions ( 5.5) ]. available data with fentanyl transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. when administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival and developmental delays at doses within the range of the human recommended dosing. no evidence of malformations were noted in animal studies completed to date [see data ]. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions ( 5.5) ]. labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. fentanyl transdermal system is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including fentanyl transdermal system, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data there are no adequate and well-controlled studies in pregnant women. fentanyl transdermal system should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures characteristic of neonatal abstinence syndrome in newborn infants. symptoms of neonatal respiratory or neurological depression were no more frequent than expected in most studies of infants born to women treated acutely during labor with intravenous or epidural fentanyl. transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. animal data no evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. the high dose was approximately 2 times the daily human dose administered by a 100 mcg/h patch on a mg/m 2 basis). in contrast, the intravenous administration of fentanyl (0, 0.01, or 0.03 mg/kg) to pregnant rats from gestation day 6 to 18 suggested evidence of embryo-toxicity and a slight increase in mean delivery time in the 0.03 mg/kg/day group (0.1 times the human dose administered by a 100 mcg/h patch on a mg/m 2 basis). there was no clear evidence of teratogenicity noted. pregnant female new zealand white rabbits were treated with fentanyl (0, 0.025, 0.1, 0.4 mg/kg) via intravenous infusion from day 6 to day 18 of pregnancy. fentanyl produced a slight decrease in the body weight of the live fetuses at the high dose, which may be attributed to maternal toxicity. under the conditions of the assay, there was no evidence for fentanyl induced adverse effects on embryo-fetal development at doses up to 0.4 mg/kg (approximately 3 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis). the potential effects of fentanyl on prenatal and postnatal development were examined in the rat model. female wistar rats were treated with 0, 0.025, 0.1, or 0.4 mg/kg/day fentanyl via intravenous infusion from day 6 of pregnancy through 3 weeks of lactation. fentanyl treatment (0.4 mg/kg/day) significantly decreased body weight in male and female pups and also decreased survival in pups at day 4. both the mid-dose and high-dose of fentanyl animals demonstrated alterations in some physical landmarks of development (delayed incisor eruption and eye opening) and transient behavioral development (decreased locomotor activity at day 28 which recovered by day 50). the mid-dose and the high-dose are 0.4 and 1.6 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis. risk summary fentanyl is excreted in human milk; therefore, fentanyl transdermal system is not recommended for use in nursing women because of the possibility of effects in their infants. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with fentanyl transdermal system. clinical considerations monitor infants exposed to fentanyl transdermal system through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions ( 6.2), clinical pharmacology ( 12.2), nonclinical toxicology ( 13.1) ]. the safety of fentanyl transdermal system was evaluated in three open-label trials in 289 pediatric patients with chronic pain, 2 years of age through 18 years of age. starting doses of 25 mcg/h and higher were used by 181 patients who had been on prior daily opioid doses of at least 45 mg/day of oral morphine or an equianalgesic dose of another opioid. initiation of fentanyl transdermal system therapy in pediatric patients taking less than 60 mg/day of oral morphine or an equianalgesic dose of another opioid has not been evaluated in controlled clinical trials. the safety and effectiveness of fentanyl transdermal system in children under 2 years of age have not been established. to guard against excessive exposure to fentanyl transdermal system by young children, advise caregivers to strictly adhere to recommended fentanyl transdermal system application and disposal instructions [see dosage and administration ( 2.7), ( 2.8) and warnings and precautions ( 5.3) ]. clinical studies of fentanyl transdermal system did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. data from intravenous studies with fentanyl suggest that the elderly patients may have reduced clearance and a prolonged half-life. moreover, elderly patients may be more sensitive to the active substance than younger patients. a study conducted with the fentanyl transdermal system patch in elderly patients demonstrated that fentanyl pharmacokinetics did not differ significantly from young adult subjects, although peak serum concentrations tended to be lower and mean half-life values were prolonged to approximately 34 hours [see clinical pharmacology ( 12.3) ]. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of fentanyl transdermal system slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.12) ]. fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. the effect of hepatic impairment on the pharmacokinetics of fentanyl transdermal system has not been fully evaluated. a clinical pharmacology study with fentanyl transdermal system in patients with cirrhosis has shown that systemic fentanyl exposure increased in these patients. because there is in-vitro and in-vivo evidence of extensive hepatic contribution to the elimination of fentanyl transdermal system, hepatic impairment would be expected to have significant effects on the pharmacokinetics of fentanyl transdermal system. avoid use of fentanyl transdermal system in patients with severe hepatic impairment [see dosage and administration ( 2.5), warnings and precautions ( 5.17) and clinical pharmacology 12.3) ]. the effect of renal impairment on the pharmacokinetics of fentanyl transdermal system has not been fully evaluated. a clinical pharmacology study with intravenous fentanyl in patients undergoing kidney transplantation has shown that patients with high blood urea nitrogen level had low fentanyl clearance. because there is in-vivo evidence of renal contribution to the elimination of fentanyl transdermal system, renal impairment would be expected to have significant effects on the pharmacokinetics of fentanyl transdermal system. avoid the use of fentanyl transdermal system in patients with severe renal impairment [see dosage and administration ( 2.6), warnings and precautions ( 5.18) and clinical pharmacology ( 12.3) ]. fentanyl transdermal system contains fentanyl, a schedule ii controlled substance. fentanyl transdermal system contains fentanyl, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions ( 5.1) ]. misuse is the intentional use, for the therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance, or physical dependence. misuse and abuse of fentanyl transdermal system increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent use of fentanyl transdermal system with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of fentanyl transdermal system abuse include those with a history of prolonged use of any opioid, including products containing fentanyl, those with a history of drug or alcohol abuse, or those who use fentanyl transdermal system in combination with other abused drugs. “drug seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. fentanyl transdermal system, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to the abuse of fentanyl transdermal system fentanyl transdermal system is intended for transdermal use only. abuse of fentanyl transdermal system poses a risk of overdose and death. this risk is increased with concurrent use of fentanyl transdermal system with alcohol and/or other cns depressants [see warnings and precautions ( 5.4), and drug interactions ( 7) ]. intentional compromise of the transdermal delivery system may result in the uncontrolled delivery of fentanyl and pose a significant risk to the abuser that could result in overdose and death [see warnings and precautions ( 5.1) ]. abuse may occur by applying the transdermal system in the absence of legitimate purpose, or by swallowing, snorting or injecting fentanyl extracted from the transdermal system. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue fentanyl transdermal system in a patient physically dependent on opioids. rapid tapering of fentanyl transdermal system in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing fentanyl transdermal system, gradually taper the dosage using a patient-specific plan that considers the following: the dose of fentanyl transdermal system the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration ( 2.9), and warnings and precautions ( 5.21) ]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations ( 8.1) ]. instructions for use fentanyl (fen' ta nil) transdermal system cii be sure that you read, understand, and follow these instructions for use before you apply fentanyl transdermal system (patch). talk to your healthcare provider or pharmacist if you have any questions. important information about the fentanyl transdermal system (patch) appearance: - fentanyl transdermal system is a rectangular, see-through patch with rounded corners. - fentanyl transdermal system comes in 5 different dosage strengths and sizes: 12 mcg/hour 25 mcg/hour 50 mcg/hour 75 mcg/hour 100 mcg/hour - 12 mcg/hour - 25 mcg/hour - 50 mcg/hour - 75 mcg/hour - 100 mcg/hour - the product name, “fentanyl”, and dosage strength are printed in green on each patch. parts of the fentanyl transdermal system patch: before applying fentanyl transdermal system - each fentanyl transdermal system patch is sealed in its own protective pouch. do not remove a fentanyl transdermal system patch from the pouch until you are ready to use it. - do not use a fentanyl transdermal system patch if the pouch seal is broken or the patch is cut, damaged or changed in any way. - fentanyl transdermal system patches are available in 5 different dosage strengths and patch sizes. make sure you have the right dose patch or patches that have been prescribed for you. - skin areas where the fentanyl transdermal system patch may be applied: for adults: put the patch on the chest, back, flank (sides of the waist), or upper arm in a place where there is no hair (see figures a-d). for children (and adults with mental impairment): put the patch on the upper back (see figure b). this will lower the chances that the child will remove the patch and put it in their mouth. for adults and children do not put a fentanyl transdermal system patch on skin that is very oily, burned, broken out, cut, irritated, or damaged in any way. avoid sensitive areas or those that move around a lot. if there is hair, do not shave (shaving irritates the skin). instead, clip hair as close to the skin as possible (see figure e). talk to your healthcare provider if you have questions about skin application sites. - put the patch on the chest, back, flank (sides of the waist), or upper arm in a place where there is no hair (see figures a-d). for children (and adults with mental impairment): - put the patch on the upper back (see figure b). this will lower the chances that the child will remove the patch and put it in their mouth. for adults and children - do not put a fentanyl transdermal system patch on skin that is very oily, burned, broken out, cut, irritated, or damaged in any way. - avoid sensitive areas or those that move around a lot. if there is hair, do not shave (shaving irritates the skin). instead, clip hair as close to the skin as possible (see figure e). - talk to your healthcare provider if you have questions about skin application sites. figure a figure b figure c figure d figure e - prepare to apply a fentanyl transdermal system patch: choose the time of day that is best for you to apply fentanyl transdermal system. change it at about the same time of day (3 days or 72 hours after you apply the patch) or as directed by your healthcare provider. do not wear more than one fentanyl transdermal system patch at a time unless your healthcare provider tells you to do so. before applying a new fentanyl transdermal system patch, remove the patch you have been wearing. clean the skin area with clear water only. pat skin completely dry . do not use anything on the skin such as soaps, lotions, oils, or alcohol before the patch is applied. - choose the time of day that is best for you to apply fentanyl transdermal system. change it at about the same time of day (3 days or 72 hours after you apply the patch) or as directed by your healthcare provider. - do not wear more than one fentanyl transdermal system patch at a time unless your healthcare provider tells you to do so. before applying a new fentanyl transdermal system patch, remove the patch you have been wearing. - clean the skin area with clear water only. pat skin completely dry . do not use anything on the skin such as soaps, lotions, oils, or alcohol before the patch is applied. - open the pouch: fold and tear at slit, or cut at slit taking care not to cut the patch. remove the fentanyl transdermal system patch. each fentanyl transdermal system patch is sealed in its own protective pouch. do not remove the fentanyl transdermal system patch from the pouch until you are ready to use it (see figure f). - peel: peel off both parts of the release liner from the patch. each fentanyl transdermal system patch has a clear plastic release liner that can be peeled off in two pieces. this covers the sticky side of the patch. carefully peel this release liner off and throw the pieces away. touch the sticky side of the fentanyl transdermal system patch as little as possible (see figure g). figure f figure g - press: press the patch onto the chosen skin site with the palm of your hand and hold there for at least 30 seconds (see figure h). make sure it sticks well, especially at the edges. fentanyl transdermal system may not stick to all people. you need to check the patch often to make sure that they are sticking well to the skin. if the patch falls off right away after applying, throw it away and put a new one on at a different skin site. see the section below called “ disposing of a fentanyl transdermal system patch.” if you have a problem with the patch not sticking apply first-aid tape only to the edges of the patch. if you continue to have problems with the patch not sticking, you may cover the patch with a transparent adhesive film dressing such as bioclusive™ or tegaderm™. these are special see-through adhesive dressings. never cover a fentanyl transdermal system patch with any other bandage or tape. remove the backing from the bioclusive™ or tegaderm™ dressing and place it carefully over the fentanyl transdermal system patch, smoothing it over the patch and your skin. if your patch falls off before 3 days (72 hours) of use, dispose of (throw away) properly. see the section below “ disposing of a fentanyl transdermal system patch.” apply a new fentanyl transdermal system patch on at a different skin site. be sure to let your healthcare provider know that this has happened, and do not replace the new patch until 3 days (72 hours) after you put it on (or as directed by your healthcare provider). - fentanyl transdermal system may not stick to all people. you need to check the patch often to make sure that they are sticking well to the skin. - if the patch falls off right away after applying, throw it away and put a new one on at a different skin site. see the section below called “ disposing of a fentanyl transdermal system patch.” - if you have a problem with the patch not sticking apply first-aid tape only to the edges of the patch. if you continue to have problems with the patch not sticking, you may cover the patch with a transparent adhesive film dressing such as bioclusive™ or tegaderm™. these are special see-through adhesive dressings. never cover a fentanyl transdermal system patch with any other bandage or tape. remove the backing from the bioclusive™ or tegaderm™ dressing and place it carefully over the fentanyl transdermal system patch, smoothing it over the patch and your skin. - apply first-aid tape only to the edges of the patch. - if you continue to have problems with the patch not sticking, you may cover the patch with a transparent adhesive film dressing such as bioclusive™ or tegaderm™. these are special see-through adhesive dressings. never cover a fentanyl transdermal system patch with any other bandage or tape. remove the backing from the bioclusive™ or tegaderm™ dressing and place it carefully over the fentanyl transdermal system patch, smoothing it over the patch and your skin. - if your patch falls off before 3 days (72 hours) of use, dispose of (throw away) properly. see the section below “ disposing of a fentanyl transdermal system patch.” apply a new fentanyl transdermal system patch on at a different skin site. be sure to let your healthcare provider know that this has happened, and do not replace the new patch until 3 days (72 hours) after you put it on (or as directed by your healthcare provider). - wash your hands when you have finished applying a fentanyl transdermal system patch. - remove a fentanyl transdermal system patch after wearing it for 3 days (72 hours). dispose of the used patch right away. see the section below “ disposing of a fentanyl transdermal system patch.” choose a different skin site to apply a new fentanyl transdermal system patch. repeat steps 2 through 6 above when applying a new fentanyl transdermal system patch. do not apply the new patch to the same place as the last one. - you can bathe, swim or shower while you are wearing a fentanyl transdermal system patch. if the patch falls off before 3 days (72 hours) after application, dispose of properly. see the section below “ disposing of a fentanyl transdermal system patch.” apply a new fentanyl transdermal system patch on a different skin site. be sure to let your healthcare provider know that this has happened, and do not replace the new patch until 3 days (72 hours) after you put it on (or as directed by your healthcare provider). disposing of a fentanyl transdermal system patch - fold the used fentanyl transdermal system patch in half so that the sticky side sticks to itself (see figure i). flush the used fentanyl transdermal system patch down the toilet right away (see figure j). a used fentanyl transdermal system patch can be very dangerous for or lead to death in babies, children, pets, and adults who have not been prescribed fentanyl transdermal system. - throw away any fentanyl transdermal system patches that are left over from your prescription as soon as they are no longer needed. remove the leftover patches from their protective pouch and remove the release liner. fold the patches in half with the sticky sides together, and flush the patches down the toilet. do not flush the pouch or the release liner down the toilet. these items can be thrown away in a trash can. figure h figure i figure j this instructions for use has been approved by the u.s. food and drug administration. manufactured by: kindeva drug delivery l.p. northridge, ca 91324 usa distributed by: alvogen, inc. pine brook, nj 07058 usa revised: 05/2023 bioclusive™ is a trademark of ethicon, inc. tegaderm™ is a trademark of 3m

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fentanyl, quantity: 6.3 mg - drug delivery system, transdermal - excipient ingredients: polyethylene terephthalate; ethyl acetate; 2-ethylhexyl acrylate; vinyl acetate; 2,2'-azobisisobutyronitrile; 2-hydroxyethyl acrylate - for the management of pain associated with cancer, palliative cancer and other conditions in patients where: - other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain, and - the pain is opioid-responsive, and - severe enough to require daily, continuous long term opioid treatment. not for use in opioid-naive patients.

United States - English - NLM (National Library of Medicine)

teva pharmaceuticals usa, inc. - fentanyl citrate (unii: mun5lyg46h) (fentanyl - unii:uf599785jz) - fentanyl 200 ug - oral transmucosal fentanyl citrate (otfc) is indicated for the management of breakthrough pain in cancer patients 16 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. patients considered opioid tolerant are those who are taking, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg of oral hydrocodone per day, or an equianalgesic dose of another opioid. patients must remain on around-the-clock opioids when taking otfc. limitations of use: - not for use in opioid non-tolerant patients. - not for use in the management of acute or postoperative pain, including headache/migraine and dental pain [see contraindications (4)] . - as a part of the tirf rems, otfc may be dispensed by outpatient pharmacies only to outpatients enrolled in the program [see  warnings and precautions  (5.7)] . for inpatient administration of otfc, patient and prescriber enrollment are not required.  oral transmucosal fentanyl citrate (otfc) is contraindicated in: - opioid non-tolerant patients: life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients [see indications and usage ( 1), warnings and precautions (5.2)]. - significant respiratory depression [see warnings and precautions (5.2 )]. - acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department [see indications and usage (1)] . - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.11 )]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.15 )]. - known hypersensitivity to fentanyl or components of otfc (e.g., anaphylaxis, hypersensitivity) [see adverse reactions (6.2)]. risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.8)] . available data with oral transmucosal fentanyl citrate (otfc) in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. there are risks to the mother and infant associated with use of otfc for an extended period of time during pregnancy (see clinical considerations). in animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. when administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival at doses within the range of the human recommended dosing. no evidence of malformations were noted in animal studies completed to date [see data] . the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset of neonatal withdrawal symptoms usually occurs in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.8)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. otfc is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including otfc, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data in women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers. transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. animal data fentanyl (25, 50, or 100 mcg/kg) citrate was administered subcutaneously to pregnant rats during the period of organogenesis (gestation day, gd 6 to 17). maternal toxicity and a decrease in fetal weights were observed at 100 mcg/kg but no teratogenicity was seen in the study (the no observed effect level of 50 mcg/kg is equivalent to 0.7 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison). fentanyl (50, 100, or 250 mcg/kg) was also administered subcutaneously to pregnant rabbits during the period of organogenesis (gd 6-18). maternal toxicity was noted at doses >100 mcg/kg. no teratogenicity was seen in the study (250 mcg/kg dose is equivalent to 3.5 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison). fentanyl has been shown to be embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.2 times the 1600 mcg dose of otfc on a mg/m2 basis) from gd 6 to 18 and 160 mcg/kg subcutaneously (1 times the 1600 mcg dose of otfc based on a mg/m2 basis). no evidence of teratogenicity was reported. no evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. the high dose was approximately 3 times the human dose of 1600 mcg otfc per pain episode on a mg/m2 basis and produced mean steady-state plasma levels that are 3.4 times higher than the mean cmax observed following administration of 1600 mcg dose of otfc in humans. in a postnatal development study, pregnant rats were treated from gd 6 through lactation day (ld) 20 with subcutaneous doses of fentanyl (25, 50, 100, and 400 mcg/kg). maternal toxicity was noted at doses >100 mcg/kg. a reduction in pup growth and delayed attainment of developmental indices were observed at >100 mcg/kg. no difference in the number of live pups/litter was seen at birth, however, pup survival at ld 4 was reduced to 48% at 400 mcg/kg and by ld 21 pup survival was reduced to 30% and 26% at 100 and 400 mcg/kg, respectively. during lactation, fentanyl-related clinical signs (decreased activity, skin cold to touch, and moribund appearance) were noted in the f1 pups, most prominently in the 400 mcg/kg group. pups from this group also had significantly reduced body weights throughout the lactation period. the dose of fentanyl administered to rats at which no developmental toxicity in the f1 generation was seen was 50 mcg/kg which is 0.6 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison. risk summary fentanyl is present in breast milk. one published lactation study reports a relative infant dose of fentanyl of 0.024%. however, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with otfc. clinical considerations monitor infants exposed to otfc through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)] . safety and effectiveness in pediatric patients below 16 years of age have not been established. in a clinical study, 15 opioid-tolerant pediatric patients with breakthrough pain, ranging in age from 5 to 15 years, were treated with otfc. the study was too small to allow conclusions on safety and efficacy in this patient population. twelve of the fifteen opioid-tolerant children and adolescents aged 5 to 15 years in this study received otfc at doses ranging from 200 mcg to 600 mcg. the mean (cv%; range) dose-normalized (to 200 mcg) cmax and auc0-8 values were 0.87 ng/ml (51%; 0.42-1.30) and 4.54 ng. h/ml (42%; 2.37-6.0), respectively, for children ages 5 to <11 years old (n = 3) and 0.68 ng/ml (72%; 0.15-1.44) and 8.38 (192%; 0.84-50.78), respectively, for children ages ≥11 to <16 y (n = 9). of the 257 patients in clinical studies of otfc in breakthrough cancer pain, 61 (24%) were 65 years of age and older, while 15 (6%) were 75 years of age and older. those patients over the age of 65 years were titrated to a mean dose that was about 200 mcg less than the mean dose titrated to by younger patients. no difference was noted in the safety profile of the group over 65 years of age as compared to younger patients in otfc clinical trials. elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously, compared with the younger population. therefore, exercise caution when individually titrating otfc in elderly patients to provide adequate efficacy while minimizing risk. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of otfc slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.11)] . fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. insufficient information exists to make recommendations regarding the use of otfc in patients with impaired renal or hepatic function. fentanyl is metabolized primarily via human cytochrome p450 3a4 isoenzyme system and mostly eliminated in urine. if the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl. both male and female opioid-tolerant patients with cancer were studied for the treatment of breakthrough cancer pain. no clinically relevant sex differences were noted either in dosage requirement or in observed adverse reactions. oral transmucosal fentanyl citrate (otfc) contains fentanyl, a schedule ii controlled substance. otfc contains fentanyl, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of otfc increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of otfc with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of otfc abuse include those with a history of prolonged use of any opioid, including products containing fentanyl, those with a history of drug or alcohol abuse, or those who use otfc in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. otfc, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of otfc abuse of otfc poses a risk of overdose and death. the risk is increased with concurrent use of otfc with alcohol and/or other cns depressants. otfc is approved for oral transmucosal use only. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)].

United States - English - NLM (National Library of Medicine)

specgx llc - fentanyl citrate (unii: mun5lyg46h) (fentanyl - unii:uf599785jz) - fentanyl 200 ug - oral transmucosal fentanyl citrate is indicated for the management of breakthrough pain in cancer patients 16 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. patients considered opioid tolerant are those who are taking, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg of oral hydrocodone per day, or an equianalgesic dose of another opioid. patients must remain on around-the-clock opioids when taking oral transmucosal fentanyl citrate. limitations of use : - not for use in opioid non-tolerant patients. not for use in opioid non-tolerant patients. - not for use in the management of acute or postoperative pain, including headache/migraine and dental pain [see contraindications (4)] . not for use in the management of acute or postoperative pain, including headache/migraine and dental pain [see contraindications (4)] . - as a part of the tirf rems, oral transmucosal fentanyl citrate may be dispensed by outpatient pharmacies only to outpatients enrolled in the program [see warnings and precautions (5.7)] . for inpatient administration of oral transmucosal fentanyl citrate, patient and prescriber enrollment are not required. as a part of the tirf rems, oral transmucosal fentanyl citrate may be dispensed by outpatient pharmacies only to outpatients enrolled in the program [see warnings and precautions (5.7)] . for inpatient administration of oral transmucosal fentanyl citrate, patient and prescriber enrollment are not required. oral transmucosal fentanyl citrate is contraindicated in: - opioid non-tolerant patients: life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients [see indications and usage (1)]; warnings and precautions (5.1) [see indications and usage (1)] . - significant respiratory depression [see warnings and precautions (5.1)] . significant respiratory depression [see warnings and precautions (5.1)] . - acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department. acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department. - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.9)] . acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.9)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.14)] . known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.14)] . - known hypersensitivity to fentanyl or components of oral transmucosal fentanyl citrate (e.g., anaphylaxis, hypersensitivity) [see adverse reactions (6.2)] . known hypersensitivity to fentanyl or components of oral transmucosal fentanyl citrate (e.g., anaphylaxis, hypersensitivity) [see adverse reactions (6.2)] . risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.8)] . available data with oral transmucosal fentanyl citrate in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. when administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival at doses within the range of the human recommended dosing. no evidence of malformations were noted in animal studies completed to date [see data] . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset of neonatal withdrawal symptoms usually occurs in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.8)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. oral transmucosal fentanyl citrate is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including oral transmucosal fentanyl citrate, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data in women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers. transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. animal data fentanyl (25, 50, or 100 mcg/kg) citrate was administered subcutaneously to pregnant rats during the period of organogenesis (gestation day, gd 6 to 17). maternal toxicity and a decrease in fetal weights were observed at 100 mcg/kg but no teratogenicity was seen in the study (the no observed effect level of 50 mcg/kg is equivalent to 0.7 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison). fentanyl (50, 100, or 250 mcg/kg) was also administered subcutaneously to pregnant rabbits during the period of organogenesis (gd 6 to 18). maternal toxicity was noted at doses >100 mcg/kg. no teratogenicity was seen in the study (250 mcg/kg dose is equivalent to 3.5 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison). fentanyl has been shown to embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.2 times the 1600 mcg dose of oral transmucosal fentanyl citrate on a mg/m2 basis) from gd 6 to 18 and 160 mcg/kg subcutaneously (1 times the 1600 mcg dose of oral transmucosal fentanyl citrate based on a mg/m2 basis). no evidence of teratogenicity was reported. no evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. the high dose was approximately 3 times the human dose of 1600 mcg oral transmucosal fentanyl citrate per pain episode on a mg/m2 basis and produced mean steady-state plasma levels that are 3.4 times higher than the mean cmax observed following administration of 1600 mcg dose of oral transmucosal fentanyl citrate in humans. in a postnatal development study, pregnant rats were treated from gd 6 through lactation day (ld) 20 with subcutaneous doses of fentanyl (25, 50, 100, and 400 mcg/kg). maternal toxicity was noted at doses >100 mcg/kg. a reduction in pup growth and delayed attainment of developmental indices were observed at >100 mcg/kg. no difference in the number of live pups/litter was seen at birth, however, pup survival at ld 4 was reduced to 48% at 400 mcg/kg and by ld 21 pup survival was reduced to 30% and 26% at 100 and 400 mcg/kg, respectively. during lactation, fentanyl-related clinical signs (decreased activity, skin cold to touch, and moribund appearance) were noted in the f1 pups, most prominently in the 400 mcg/kg group. pups from this group also had significantly reduced body weights throughout the lactation period. the dose of fentanyl administered to rats at which no developmental toxicity in the f1 generation was seen was 50 mcg/kg which is 0.6 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison. risk summary fentanyl is present in breast milk. one published lactation study reports a relative infant dose of fentanyl of 0.024%. however, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with oral transmucosal fentanyl citrate. clinical considerations monitor infants exposed to oral transmucosal fentanyl citrate through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)] . safety and effectiveness in pediatric patients below 16 years of age have not been established. in a clinical study, 15 opioid-tolerant pediatric patients with breakthrough pain, ranging in age from 5 to 15 years, were treated with oral transmucosal fentanyl citrate. the study was too small to allow conclusions on safety and efficacy in this patient population. twelve of the fifteen opioid-tolerant children and adolescents aged 5 to 15 years in this study received oral transmucosal fentanyl citrate at doses ranging from 200 mcg to 600 mcg. the mean (cv%; range) dose-normalized (to 200 mcg) cmax and auc0-8 values were 0.87 ng/ml (51%; 0.42-1.30) and 4.54 ng•h/ml (42%; 2.37-6.0), respectively, for children ages 5 to <11 years old (n = 3) and 0.68 ng/ml (72%; 0.15-1.44) and 8.38 (192%; 0.84-50.78), respectively, for children ages ≥11 to <16 y (n = 9). of the 257 patients in clinical studies of oral transmucosal fentanyl citrate in breakthrough cancer pain, 61 (24%) were 65 years of age and older, while 15 (6%) were 75 years of age and older. those patients over the age of 65 years were titrated to a mean dose that was about 200 mcg less than the mean dose titrated to by younger patients. no difference was noted in the safety profile of the group over 65 years of age as compared to younger patients in oral transmucosal fentanyl citrate clinical trials. elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously, compared with the younger population. therefore, exercise caution when individually titrating oral transmucosal fentanyl citrate in elderly patients to provide adequate efficacy while minimizing risk. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of oral transmucosal fentanyl citrate slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.9)] . fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. insufficient information exists to make recommendations regarding the use of oral transmucosal fentanyl citrate in patients with impaired renal or hepatic function. fentanyl is metabolized primarily via human cytochrome p450 3a4 isoenzyme system and mostly eliminated in urine. if the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl. both male and female opioid-tolerant cancer patients were studied for the treatment of breakthrough cancer pain. no clinically relevant sex differences were noted either in dosage requirement or in observed adverse reactions. oral transmucosal fentanyl citrate contains fentanyl, a schedule ii controlled substance. oral transmucosal fentanyl citrate contains fentanyl, a substance with a high potential for abuse similar to other opioids including hydrocodone, hydromorphone, methadone, morphine oxycodone, oxymorphone, and tapentadol. oral transmucosal fentanyl citrate can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.6)] . all patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. oral transmucosal fentanyl citrate, like other opioids, can be diverted for non-medical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to the abuse of oral transmucosal fentanyl citrate oral transmucosal fentanyl citrate is for oral transmucosal use only. abuse of oral transmucosal fentanyl citrate poses a risk of overdose and death. the risk is increased with concurrent abuse of oral transmucosal fentanyl citrate with alcohol and other central nervous system depressants. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)] .

United States - English - NLM (National Library of Medicine)

par pharmaceutical inc. - fentanyl (unii: uf599785jz) (fentanyl - unii:uf599785jz) - fentanyl 25 ug in 1 h - fentanyl transdermal system is contraindicated in the following patients and situations: clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see warnings precautions (5.4)]. teratogenic effects pregnancy c: there are no adequate and well-controlled studies in pregnant women. fentanyl transdermal system should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. the potential effects of fentanyl on embryo-fetal development were studied in the rat, mouse, and rabbit models. published literature reports that administration of fentanyl (0, 10, 100, or 500 mcg/kg/day) to pregnant female sprague-dawley