- [Effect of enterostomy on analgesic pattern in patients with advanced digestive tract cancer]. [Journal Article]Zhonghua Wei Chang Wai Ke Za Zhi 2019; 22(12):1159-1164ZW
- CONCLUSIONS: Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.
- [French trends in the misuse of Fentanyl: From 2010 to 2015]. [Journal Article]Therapie 2019T
- CONCLUSIONS: Our results report significant and worrying misuse of transmucosal fentanyl formulations with wide off-label use and also primary dependence on fentanyl, regardless of galenic formulation, in patients treated for chronic non cancer pain. Given the significant risks of fentanyl, it is necessary to continue the monitoring of misuse, in particular, thanks to the activities of the French Addictovigilance network allowing a multisource approach and who provides information concerning cases of abuse, misuse and dependence.
- Raman mapping of fentanyl transdermal delivery systems with off-label modifications. [Journal Article]Analyst 2019A
- Raman mapping is a powerful and emerging tool in characterization of pharmaceuticals and provides non-destructive chemical and structural identification with minimal sample preparation. One pharmaceutical form that is suitable but has not been studied in-depth with Raman mapping is transdermal delivery systems (TDS). TDS are dosage forms designed to deliver a therapeutically effective amount of a…
Raman mapping is a powerful and emerging tool in characterization of pharmaceuticals and provides non-destructive chemical and structural identification with minimal sample preparation. One pharmaceutical form that is suitable but has not been studied in-depth with Raman mapping is transdermal delivery systems (TDS). TDS are dosage forms designed to deliver a therapeutically effective amount of active pharmaceutical ingredient (API) across a patient's skin. To enhance drug delivery through the skin, the API in the formulation is often close to a saturated or supersaturated state. Thus, improper use or off-label modifications can lead to occurrence of unwanted API changes, specifically, crystallization over time. Here, off-label modifications were mimicked on a set of fentanyl drug-in-adhesive TDS sold on the U.S. market by four different manufacturers via die cutting, and then the die cut TDS were investigated through confocal Raman mapping for structural and chemical changes. Using Multivariate Curve Resolution (MCR), not only was morphological and chemical characterization of transdermal systems provided, but also fentanyl crystals in certain products due to off-label modifications were identified. The chemometric model used in analysis of Raman maps allowed precise identification of fentanyl as the crystalline material as confirmed by the hit-quality-index correlation of component spectra from the chemometric model with library spectra of a fentanyl reference standard. The results show that confocal Raman mapping with MCR can be utilized in assessing pharmaceutical quality of TDS. This method has the potential to be widely used in characterization of such systems as an alternative to existing techniques.
- [Quasi-experimental study of an intervention on the pharmacological management of non-oncological chronic pain in Primary Care]. [Journal Article]Aten Primaria 2019AP
- CONCLUSIONS: The intervention reduced the number of patients with incidences, and this reduction was higher in the prospective cohort, confirming the efficacy of sending information about patients with incidences to their physicians. The incorporation of new treatments during the follow-up year was significant, so these interventions should be perpetuated over time.
- Fentanyl assisted treatment: a possible role in the opioid overdose epidemic? [Letter]Subst Abuse Treat Prev Policy 2019; 14(1):50SA
- CONCLUSIONS: There are known limitations to existing OAT options and there is a need to urgently evaluate alternative strategies for patients who are using illicit fentanyl not successfully treated with conventional OAT. Many patients may be attracted to, and retained in, fentanyl assisted treatment. This may be another strategy for certain patients to prevent harms caused by illicit fentanyl use, including overdose and death.
- Identifying risks areas related to medication administrations - text mining analysis using free-text descriptions of incident reports. [Journal Article]BMC Health Serv Res 2019; 19(1):791BH
- CONCLUSIONS: Interventions to increase medication administration safety should focus on checking patient allergies and medication doses, especially for intravenous and transdermal medications. High-risk medications include insulin, analgesics, antibacterial drugs, anticoagulants, and potassium chloride. Text mining may be useful for analysing large free text datasets and should be developed further.
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury: Opioids [BOOK]National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda (MD)BOOK
- The opioids are a large class of medications related in structure to the natural plant alkaloids found in opium that are derived from the resin of the opium poppy, Papaver somniferum. The natural alkaloids are also referred to as opiates and include morphine and codeine. Synthetic derivatives include heroin, fentanyl, hydromorphone, methadone, buprenorphine and others. The opioids are highly pote…
The opioids are a large class of medications related in structure to the natural plant alkaloids found in opium that are derived from the resin of the opium poppy, Papaver somniferum. The natural alkaloids are also referred to as opiates and include morphine and codeine. Synthetic derivatives include heroin, fentanyl, hydromorphone, methadone, buprenorphine and others. The opioids are highly potent and effective analgesics, but most have a high potential for dependency and abuse. Opioids act by engagement of specific cell surface receptors; the opiate receptors, which are designated µ [mu], κ [kappa] and δ [delta]. These receptors are found predominantly in the central nervous system, brain and spinal column, but are also present on vascular, cardiac, lung, gut and even peripheral blood mononuclear cells. Engagement of the opiate receptors generates a series of intracellular signals, including inhibition of adenylate cyclase, decreased opening of calcium channels, increased potassium currents and activation of protein kinase C (PKC). The major effect of these pathways is reduction in cell excitability and neurotransmission. The natural ligands for the opiate receptors are the so-called endogenous opioid peptides such as the enkephalins, endorphins and endomorphins. The opioids have a variety of clinical effects, but are predominantly known and used for their profound pain relieving effects. Other effects that are often linked to opiate analgesia include euphoria, changes in mood, drowsiness and mental clouding. However, the distinctive feature of the analgesia induced by the opioids is the lack of loss of consciousness. The pain is often described as less intense, but still present although better tolerated. Thus, the opioids do not decrease or treat the cause of the painful stimulus, but rather decrease its perception. Other effects of opioids include respiratory depression, decreased gastrointestinal motility, sedation, nausea, vomiting, constipation and intestinal bloating. Opioids also have direct cardiovascular effects, decreasing blood pressure, causing vasodilation and decreasing cardiac work. Most opioids have similar effects and side effects, although pharmacokinetic differences, tissue distribution, and receptor type specificity probably account for the variation in effects of the various synthetic and semisynthetic derivatives of morphine. Morphine is considered the prototype opiate, against which other agents are measured for their analgesic effects as well as adverse side effects. The opioids can be categorized into subclasses on the basis of their chemical structure as opium alkaloids (opiates: codeine, morphine), semisynthetic derivatives of the natural alkaloids (hydrocodone, hydromorphone, oxycodone, buprenorphine), and various classes of synthetic opioids such as the anililopiperidines (fentanyl, alfentanil, sufentanil, remifentanil), diphenylpropylamine derivatives (propoxyphene, dextropropoxyphene, methadone, diphenoxylate, loperamide), and others (pentazocine, butorphanol, nalbupine, levorphanol, tramadol), and, the opioid antagonists (nalmefene, naloxone and naltrexone). They can also be informally classified based upon their major use such as anesthesia (fentanyl, alfentanil, remifentanil, sufentanil), severe pain (morphine, hydromorphone, levorphanol, merperidine), moderate to severe acute or chronic pain (transdermal or transbuccal fentanyl, codeine, oxycodone, hydrocodone, levorphanol, methadone), diarrhea (loperamide, diphenoxylate), and cough (codeine, hydrocodone). Finally, opioids can be categorized on the basis of their action as full agonists, partial agonists or mixed agonists/antagonists, and antagonists of opiate receptors. Opioid receptor antagonists are used to reverse the effects of opioids and are invaluable in the management of opioid overdose (naloxone, naltrexone, nalmifene). Specialized opioid antagonists can be used to reverse unwanted opioid effects, such as constipation in patients with chronic pain on long-term opioids. These agents (naldemedine, naloxegol) are generally modified so as not to cross the blood brain and reverse the central nervous system effects of opiates. Opioids are rare causes of drug induced liver disease and are not mentioned in large case series of clinically apparent liver injury caused by medications. In physiological, pain relieving doses, opioids have not been implicated in causing clinically apparent liver injury, acute liver failure, chronic hepatitis or vanishing bile duct syndrome. However, overdoses of the more potent opioids have been linked to cases of acute liver injury, usually with a precipitous onset and pattern of acute toxicity with marked elevations in serum aminotransferase levels and early onset of signs of hepatic failure. This syndrome has been best characterized after buprenorphine overdose or abuse, but likely occurs with others. It is possible that the implicated opioids are not directly toxic to the liver, but cause ischemic liver injury due to respiratory failure, cardiovascular collapse, shock and anoxia that can occur with severe opioid overdose. The clinical syndrome resembles acute hepatic necrosis and liver failure, but is rapidly reversible and rarely the primary cause of death from overdose. A special form of liver injury linked to opioid use occurs with their fixed drug combinations with acetaminophen. These combinations are commonly used for moderate to moderately severe pain and can lead to abuse. If taken too frequently, acetaminophen doses may reach toxic levels, particularly with overuse for several days in the face of malnutrition, alcohol abuse or intercurrent illness. These other stresses can lower hepatic glutathione levels and predispose to acetaminophen hepatotoxicity. This constellation of events is referred to as inadvertent or unintended acetaminophen overdose or more colloquially as a “therapeutic misadventure”. For this reason, the FDA has recommended that physicians not use opioid combinations in which the dose of acetaminophen is greater than 325 mg per tablet or unit dose. References to the safety and hepatotoxic potential of the various opiate agonists are given together at the end of this Overview section. References to the opioids and the opiate antagonists used to treat substance abuse are given separately with each agent (buprenorphine, methadone, nalmefene, naloxone, naltrexone). The opioids are discussed individually or as groups of agents and links to each are given below. Full and partial agonists: Alfentanil. Butorphanol. Codeine. Diphenoxylate. Fentanyl. Heroin. Hydrocodone. Hydromorphone. Levorphanol. Loperamide. Meperidine. Methadone. Morphine. Opium. Oxycodone. Oxymorphone. Pentazocine. Remifentanil. Sufentanil. Tramadol. Opiate antagonists: Naldemedine. Nalmefene. Naloxegol. Naloxone. Naltrexone.
- Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients. [Journal Article]Sci Rep 2019; 9(1):14635SR
- Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinic…
Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1'-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination.
- Does transdermal fentanyl work in patients with low BMI? Patient-reported outcomes of pain and percent pain relief in cancer patients on transdermal fentanyl. [Journal Article]Cancer Med 2019; 8(18):7516-7522CM
- CONCLUSIONS: When predicting percent pain relief, we conclude that there is no basis for avoiding TDF or modifying its dose in cancer patients with low BMI and cachexia.
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- Transdermal fentanyl to parenteral morphine route switch and drug rotation in refractory cancer cachexia. [Journal Article]BMJ Support Palliat Care 2019BS
- It is recommended not to use transdermal fentanyl (Fe) patches (TFP) in cancer cachexia but TFP may be the only available option for pain. Limited evidence suggests lower Fe absorption from TFP in cachexia. We describe a case of metastatic breast cancer with refractory cachexia. Her pain was uncontrolled on TFP and was route switched and drug rotated to intravenous morphine (M). We were conservat…
It is recommended not to use transdermal fentanyl (Fe) patches (TFP) in cancer cachexia but TFP may be the only available option for pain. Limited evidence suggests lower Fe absorption from TFP in cachexia. We describe a case of metastatic breast cancer with refractory cachexia. Her pain was uncontrolled on TFP and was route switched and drug rotated to intravenous morphine (M). We were conservative and did not use the 1:100 TFP to oral M conversion ratio. Assuming opioid needs were similar before and after switch/rotation, the suitable conversion ratio in this case was about 1:25. Absent clear guidelines on converting from TFP in cachexia, it is better to avoid TFP. When essential to use TFP in cachexia, caution should be taken when switching from TFP to avoid overdose.