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OBJECTIVE: An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management. METHODS: The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine. RESULTS: The panel recommended that buprenorphine's classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended that buprenorphine be considered before some Schedule II, III, or IV opioids in patients with a favorable risk/benefit profile on the basis of metabolic factors, abuse potential, and tolerability and that buprenorphine be continued during the perioperative/trauma period. In addition, switching patients from a full µ-opioid receptor agonist to buprenorphine should be considered with no weaning period at starting doses that are based on the previous opioid dose. CONCLUSIONS: These recommendations provide a framework for clinicians to address most clinical scenarios regarding buprenorphine use. The overall consensus of the panel was that buprenorphine is a unique Schedule III opioid with favorable pharmacologic properties and a safety profile that may be desirable for chronic pain management.
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Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Dor Crônica/tratamento farmacológico , Substituição de Medicamentos/métodos , Humanos , Guias de Prática Clínica como Assunto , Receptores Opioides mu/agonistasRESUMO
OBJECTIVE: To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP). DESIGN: Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (â¼14 days after the last dose of NKTR-181). SETTING: Multicenter, long-term clinical research study. METHODS: NKTR-181 administered at doses of 100-600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF). RESULTS: The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events. CONCLUSIONS: The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.
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Dor Crônica , Dor Lombar , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Método Duplo-Cego , Humanos , Dor Lombar/tratamento farmacológico , Morfinanos , Medição da Dor , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist. DESIGN: Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP). SETTING: Conducted in the United States at multiple sites. METHODS: SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events. RESULTS: Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo). CONCLUSIONS: NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.
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Dor Lombar , Morfinanos , Analgésicos , Analgésicos Opioides , Animais , Método Duplo-Cego , Feminino , Humanos , Dor Lombar/tratamento farmacológico , Suínos , Resultado do TratamentoRESUMO
Objective: To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. Methods: An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Results: Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from validated risk assessment tools, and previous UDM. Urine drug monitoring is suggested to be performed at baseline for most patients prescribed opioids for chronic pain and at least annually for those at low risk, two or more times per year for those at moderate risk, and three or more times per year for those at high risk. Additional UDM should be performed as needed on the basis of clinical judgment. Conclusions: Although evidence on the efficacy of UDM in preventing opioid use disorder, overdose, and diversion is limited, UDM is recommended by the panel as part of ongoing comprehensive risk monitoring in patients prescribed opioids for chronic pain.
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Analgésicos Opioides/efeitos adversos , Monitoramento de Medicamentos/métodos , Overdose de Drogas/prevenção & controle , Overdose de Drogas/urina , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Detecção do Abuso de Substâncias/métodos , Analgésicos Opioides/urina , Dor Crônica/tratamento farmacológico , Consenso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/urina , Uso Excessivo de Medicamentos PrescritosAssuntos
Fentanila/urina , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Detecção do Abuso de Substâncias/estatística & dados numéricos , COVID-19 , Prescrições de Medicamentos/estatística & dados numéricos , Fentanila/uso terapêutico , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: Millions of patients continue to require opioid analgesics for control of moderate to severe chronic pain, which is a disease that affects more Americans than cancer, heart disease, and diabetes combined. Common opioid adverse effects include constipation, sedation, and nausea. A lesser-known sequelae is opioid induced androgen deficiency (OPIAD). The objective of this review was to better characterize the effects of opioids on the endocrine system. METHODS: Published data were evaluated to identify links between opioid use and hypogonadism, as well as to describe proposed physiological mechanisms. RESULTS: Chronic opioid use may predispose to hypogonadism through alteration of the hypothalamic-pituitary-gonadal axis as well as the hypothalamic-pituitary-adrenal-axis. The resulting hypogonadism and hypotestosteronism may contribute to impaired sexual function, decreased libido, infertility, and osteoporosis- none of which may be clinically recognized as opioid related. CONCLUSIONS: OPIAD is a recognized consequence of long-term opioid therapy. Patients initiated or maintained on opioids should be queried about symptoms that might suggest hypogonadism including irregular menses, reduced libido, depression, fatigue, and hot flashes or night sweats. Some clinicians recommend assessment of baseline testosterone levels prior to initiating therapy. Additional data appear necessary to formulate guidelines regarding the diagnosis and management of OPIAD. Options include, rotating, reducing the dose or type, or cessation of opioid therapy or adding hormonal supplementation in the form of androgen replacement therapy. There are multiple formulations of testosterone available for replacement therapy, which is usually guided by laboratory measurements.
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Analgésicos Opioides/uso terapêutico , Doenças do Sistema Endócrino/tratamento farmacológico , Hipogonadismo/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , HumanosRESUMO
OBJECTIVE: Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy. METHODS: A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique. RESULTS: Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC-SYM, and 28-item PAC-QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation. CONCLUSIONS: The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid-induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first-line interventions.
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Analgésicos Opioides/efeitos adversos , Constipação Intestinal/diagnóstico , Constipação Intestinal/tratamento farmacológico , Prescrições de Medicamentos/normas , Guias de Prática Clínica como Assunto , Inquéritos e Questionários/normas , Constipação Intestinal/induzido quimicamente , Esquema de Medicação , Humanos , Estados UnidosRESUMO
The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion. Unintentional misuse may also occur when ER formulations are manipulated for medicinal administration, such as crushing a dose for easier oral intake. As part of a multipronged strategy designed to fight the opioid epidemic, abuse-deterrent formulations (ADFs) were developed to deter misuse, abuse, and diversion of opioids by making manipulation more difficult and nonoral routes of administration less rewarding. Although ADF opioids have been shown to decrease rates of abuse and diversion, they are not equally effective in terms of deterring manipulation for abuse or misuse. Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions. ADF utilization has been hampered by patient access issues, including high prices due to lack of insurance coverage. Postmarket real-world studies demonstrate lower rates of abuse, misuse, and diversion for ADF ER opioids compared with non-ADF formulations. However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs.
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Objective: This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment. Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period. Subjects: The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week. Results: Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week. Conclusion: In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO.
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Importance: No safe level of exposure to lead has been identified. Objective: To evaluate individual- and community-level factors associated with detectable and elevated blood lead levels (BLLs) in children. Design, Setting, and Participants: This cross-sectional, retrospective study analyzed deidentified results from blood lead tests performed at a large clinical laboratory from October 1, 2018, to February 29, 2020. Participants were 1â¯141â¯441 children younger than 6 years living in all 50 US states and the District of Columbia who underwent blood lead testing during the study period. Children who underwent lead testing of unknown source and those with elevated BLLs who received capillary blood lead testing without confirmatory venous testing were excluded. Exposures: Individual demographic categories included sex, age, and insurance type; community-level demographic categories included pre-1950s housing, poverty, predominant race and ethnicity, and geographical regions. Main Outcomes and Measures: Proportions of children with detectable (≥1.0 µg/dL) and elevated (≥5.0 µg/dL) BLLs, by exposure category. Results: Of the 1â¯141â¯441 children (586â¯703 boys [51.4%]; mean [SD] age, 2.3 [1.4] years) in the study, more than half of the children tested (576â¯092 [50.5%; 95% CI, 50.4%-50.6%]) had detectable BLLs, and 21â¯172 children (1.9% [95% CI, 1.8%-1.9%]) had BLLs of 5.0 µg/dL or more. In multivariable analyses, children with public insurance had greater odds of having detectable BLLs (adjusted odds ratio [AOR], 2.01 [95% CI, 1.99-2.04]) and elevated BLLs (AOR, 1.08 [95% CI, 1.04-1.12]). The proportion of children with detectable and elevated BLLs increased significantly for progressive pre-1950s housing and poverty quintiles (P < .001). The odds of detectable BLLs were significantly higher among children in the highest vs lowest quintile of pre-1950s housing (AOR, 1.65 [95% CI, 1.62-1.68]) and of poverty (AOR, 1.89 [95% CI, 1.86-1.93]). A similar association was found for those with elevated BLLs, with an AOR of 3.06 (95% CI, 2.86-3.27) for the highest vs lowest quintile of pre-1950 housing and 1.99 (95% CI, 1.88-2.11) for the highest quintile of poverty. Children residing in zip codes with predominantly Black non-Hispanic and non-Latinx populations had higher odds of detectable BLLs (AOR, 1.13 [95% CI, 1.11-1.15]) but lower odds for elevated BLL (AOR, 0.83 [95% CI, 0.80-0.88]). Conclusions and Relevance: This study suggests that, despite progress in reducing pediatric lead exposure, substantial individual- and community-level disparities persist.
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Intoxicação por Chumbo , Chumbo/sangue , Características de Residência , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Estados UnidosRESUMO
The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks. Among individuals tested, positivity increased by 35% for non-prescribed fentanyl and 44% for heroin during the pandemic. Positivity for non-prescribed fentanyl increased significantly among patients positive for other drugs: by 89% for specimens positive for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < 0.01 for all comparisons). These findings suggest significant increases in dangerous drug combinations. Positivity for non-prescribed use of many other drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. Models adjusting for potential confounding variables, including medication-assisted treatment and treatment at a substance use disorder facility indicated that the risk for non-prescribed fentanyl positivity rose by more than 50% during the pandemic. In summary, these findings demonstrate decreased drug testing overall, with increased positivity for high-risk drugs and dangerous drug combinations. The convergence of the drug abuse epidemic and COVID-19 pandemic has led to an increased need for health care and public health resources dedicated to supporting vulnerable patients and addressing the underlying causes of these disturbing trends.
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COVID-19 , Epidemia de Opioides/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides , Detecção do Abuso de Substâncias/estatística & dados numéricos , Adolescente , Adulto , Idoso , Analgésicos Opioides/urina , Feminino , Fentanila/urina , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Pandemias , SARS-CoV-2 , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto JovemRESUMO
PURPOSE: The primary objective was to evaluate adhesion performance of the lidocaine topical system 1.8% for 12 hours in healthy human subjects in three studies: as a single product (Study 1) and versus other lidocaine topical products (lidocaine patch 5% and lidocaine medicated plaster 5% [Study 2] and generic lidocaine patch 5% [Study 3]). Safety of the lidocaine topical system 1.8%, with a skin irritation focus, was a secondary objective. PATIENTS AND METHODS: All three studies were open-label, randomized, Phase 1 adhesion performance studies in healthy adult volunteers (N=125). Lidocaine topical products were applied for 12 hours per test, per study arm. Adhesion of all test products was scored at 0, 3, 6, 9, and 12 hours post-application. Skin irritation was scored after product removal or when a product detached. RESULTS: Overall, the majority (≥75%) of subjects treated with the lidocaine topical system 1.8% demonstrated ≥90% adhesion (FDA adhesion score 0) throughout the 12-hour administration period versus 13.6% of subjects treated with lidocaine patch 5%, 15.9% of subjects treated with lidocaine medicated plaster 5%, and 0% of subjects treated with the generic lidocaine patch 5%. There were no complete detachments with the lidocaine topical system 1.8%, whereas 4.5% of lidocaine patch 5% and lidocaine medicated plaster 5% detached, and 29% of generic lidocaine patch 5% detached. Minimal skin irritation was observed with each lidocaine topical product. CONCLUSION: Across three studies, lidocaine topical system 1.8% demonstrated superior adhesion performance versus the three other products tested. Skin irritation was minimal across products and studies. CLINICALTRIALSGOV: NCT04312750, NCT04320173, NCT04319926.
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Traditionally, musculoskeletal pain management has focused on the use of conventional treatments to relieve pain. However, multi-modal integrative medicine including alternative/complementary treatments is becoming more widely used and integrated into treatment guidelines around the world. The uptake of this approach varies according to country, with generally a higher uptake in developed countries and in females aged more than 40 years. Integral to the concept described here, is that the body has an innate ability to self-heal, which can be optimized by the use of integrative medical strategies. Stress triggers for acute or recurring musculoskeletal pain are diverse and can range from physical to psychological. The mechanism by which the body responds to triggers and initiates the self-healing processes is complex, but five body networks or processes are thought to be integral: the nervous system, microcirculation/vasodilation, immune modulation, muscular relaxation/contraction and psychological balance. Multi-modal integrative medicine approaches include nutritional/dietary modification, postural/muscular training exercises, and cognitive behavioral mind/body techniques. This article will review the self-healing concept and provide plausible scientific evidence where available.
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Opioids can be an effective treatment option for appropriate patients with chronic pain for whom nonpharmacological or nonopioid treatment does not provide adequate pain relief. However, extended-release (ER) opioid formulations, because of their high drug content, are attractive options for nonmedical use and abuse. Xtampza® ER (oxycodone DETERx®) capsules, an ER abuse-deterrent formulation (ADF), contain microspheres that combine oxycodone with inactive ingredients to increase the difficulty of tampering with the ER mechanism. The aim of this article is to review five previously published studies highlighting the impact of physical manipula-tion (ie, crushing and chewing) on the pharmacokinetic (PK) properties of orally administered Xtampza ER compared with immedi-ate-release (IR) oxycodone and/or reformulated OxyContin® (the first approved oxycodone ER ADF). Across five studies, manipulated (crushed or chewed) Xtampza ER retained an ER PK profile similar to that of intact Xtampza ER, with respect to maximum plasma con-centration (Cmax) and time to Cmax. Additionally, bioequivalence was established between manipulated and intact Xtampza ER, based on Cmax and area under the concentration-time curve values in healthy volunteers and nondependent recreational opioid users. In contrast, crushed OxyContin failed to retain the ER PK profile of intact OxyContin and was bioequivalent to IR oxycodone, based on Cmax in healthy volunteers. The retention of ER PK properties when capsule contents are physically manipulated before oral administra-tion suggests Xtampza ER has lower potential to be manipulated for oral abuse when compared with IR oxycodone or OxyContin.
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Analgésicos Opioides , Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Oxicodona , Analgésicos Opioides/química , Analgésicos Opioides/farmacocinética , Preparações de Ação Retardada , Humanos , Oxicodona/química , Oxicodona/farmacocinéticaRESUMO
Topical and transdermal formulations are a common means of pharmaceutical drug delivery. If a drug is able to penetrate transcutaneously, the skin is an ideal site for the delivery of medications for both local (topical) and systemic (transdermal) effects. The administration of analgesics through the skin poses several potential advantages to those administered orally including compliance, the ability to deliver a drug to a peripheral target site and more stable and sustained plasma levels. One method of drug delivery is with the use of patch formulations - also known as patch systems. Typically, transdermal patches deliver medications intended to reach the systemic circulation, whereas topical patches are designed to keep medication localized for targeted delivery in proximity to the application site. There are a variety of technologies and materials utilized in patches, as well as penetration and formulation enhancers that ultimately affect the performance, efficacy and safety of the patch system. The degree of adherence to the skin is also of critical importance in drug delivery. Patches that lift up or fall off before the prescribed time period may represent a therapeutic failure and must be replaced, increasing patch utilization and cost to the healthcare system or to the patient. The added risk from accidental exposure makes poor patch adhesion a safety issue as well. A variety of analgesics are currently available as patch formulations including local anesthetics, capsaicin, nonsteroidal anti-inflammatory drugs and opioids. This review will highlight each of those patch delivery systems and introduce newer patch technologies that lend towards improved adhesion and compliance. Understanding the designs, limitations and benefits of patch systems will allow clinicians to select between these therapies when appropriate for their patients.
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Buprenorphine is a Schedule III opioid analgesic with unique pharmacodynamic and pharmacokinetic properties that may be preferable to those of Schedule II full µ-opioid receptor agonists. The structure of buprenorphine allows for multimechanistic interactions with opioid receptors µ, δ, κ, and opioid receptor-like 1. Buprenorphine is considered a partial agonist with very high binding affinity for the µ-opioid receptor, an antagonist with high binding affinity for the δ- and κ-opioid receptors, and an agonist with low binding affinity for the opioid receptor-like 1 receptor. Partial agonism at the µ-opioid receptor does not provide partial analgesia, but rather analgesia equivalent to that of full µ-opioid receptor agonists. In addition, unlike full µ-opioid receptor agonists, buprenorphine may have a unique role in mediating analgesic signaling at spinal opioid receptors while having less of an effect on brain receptors, potentially limiting classic opioid-related adverse events such as euphoria, addiction, or respiratory depression. The pharmacokinetic properties of buprenorphine are also advantageous in a clinical setting, where metabolic and excretory pathways allow for use in patients requiring concomitant medications, the elderly, and those with renal or hepatic impairment. The unique pharmacodynamic and pharmacokinetic properties of buprenorphine translate to an effective analgesic with a potentially favorable safety profile compared with that of full µ-opioid receptor agonists for the treatment of chronic pain.
The unique pharmacodynamic and pharmacokinetic properties of the Schedule III opioid buprenorphine contribute to its effective pain relief and a potentially favorable safety profile for chronic pain management.
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Opioid analgesics remain a treatment option for refractory acute and chronic pain, despite their potential risk for abuse and adverse events (AEs). Opioids are associated with several common AEs, but the most bothersome is opioid-induced constipation (OIC). OIC is often overlooked but has the potential to affect patient quality of life, increase associated symptom burden, and impede long-term opioid compliance. The peripherally acting µ-receptor antagonists (PAMORAs) are a class of drugs that include methylnaltrexone, naloxegol, and naldemedine. Collectively, each is approved for the treatment of OIC. PAMORAs work peripherally in the gastrointestinal tract, without impacting the central analgesic effects of opioids. However, each has unique pharmacokinetic properties that may be impacted by coadministered drugs or food. This review focuses on important metabolic and pharmacokinetic principals that are pertinent to drug interactions involving µ-opioid receptor antagonists prescribed for OIC. It highlights subtle differences among the PAMORAs that may have clinical significance. For example, unlike naloxegol or naldemedine, methylnaltrexone is not a substrate for CYP3A4 or p-glycoprotein; therefore, its plasma concentration is not altered when coadministered with concomitant medications that are CYP3A4 or p-glycoprotein inducers or inhibitors. With a better understanding of pharmacokinetic nuances of each PAMORA, clinicians will be better equipped to identify potential safety and efficacy considerations that may arise when PAMORAs are coadministered with other medications.
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Health-care professionals are faced with a daunting task: balancing appropriate care for chronic pain with their responsibility to keep patients and others safe from treatment-related harm. Whereas opioids have historically been considered an effective tool in the analgesic armamentarium, the rise of opioid abuse has caused the pendulum to swing away from prescribing opioids to an emphasis on safety. This paradigm shift risks neglecting the very real consequences of untreated/undertreated pain. Using data from the medical literature, this review examines influences on the real and perceived benefit-to-risk ratio for opioids and provides clinicians with a practical approach to prescribing opioids that minimizes the risk for abuse/misuse. There is appreciable clinical trial and observational evidence of efficacy/effectiveness with opioids used for pain management over the short or long term when considered in the context of pharmacologic alternatives. Enhancing the relative safety and minimizing the risk for abuse/misuse may be achieved through proactive prescription practices that include careful patient selection, risk assessment, individualized and multimodal treatment plans with established goals, initiating opioid treatment cautiously with an exit plan in place, ongoing assessments of response to therapy, and routine patient monitoring. Additionally, prescribing opioids with a lower potential for abuse or misuse (e.g. abuse-deterrent formulations) may provide a benefit. Using a pragmatic approach to prescribing practices, we postulate that the balance between benefit and risk can be favorable for opioid therapy in select patients, even for long-term treatment of chronic pain.
Assuntos
Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Humanos , Manejo da Dor , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Medição de RiscoRESUMO
The continued prevalence of chronic low back pain (CLBP) is a testament to our lack of understanding of the potential causes, leading to significant treatment challenges. CLBP is the leading cause of years lived with disability and the fifth leading cause of disability-adjusted life-years. No single non-pharmacologic, pharmacologic, or interventional therapy has proven effective as treatment for the majority of patients with CLBP. Although non-pharmacologic therapies are generally helpful, they are often ineffective as monotherapy and many patients lack adequate access to these treatments. Noninvasive treatment measures supported by evidence include physical and chiropractic therapy, yoga, acupuncture, and non-opioid and opioid pharmacologic therapy; data suggest a moderate benefit, at most, for any of these therapies. Until our understanding of the pathophysiology and treatment of CLBP advances, clinicians must continue to utilize rational multimodal treatment protocols. Recent Centers for Disease Control and Prevention guidelines for opioid prescribing recommend that opioids not be utilized as first-line therapy and to limit the doses when possible for fear of bothersome or dangerous adverse effects. In combination with the current opioid crisis, this has caused providers to minimize or eliminate opioid therapy when treating patients with chronic pain, leaving many patients suffering despite optimal nonopioid therapies. Therefore, there remains an unmet need for effective and tolerable opioid receptor agonists for the treatment of CLBP with improved safety properties over legacy opioids. There are several such agents in development, including opioids and other agents with novel mechanisms of action. This review critiques non-pharmacologic and pharmacologic treatment modalities for CLBP and examines the potential of novel opioids and other analgesics that may be a useful addition to the treatment options for patients with chronic pain.
RESUMO
PURPOSE: Pain is the most common reason for patients to consult primary care providers. Identification of effective treatments with minimal adverse events is critical to safer opioid-sparing and multi-modal approaches to pain treatment. Topical analgesic patches target medication to peripheral sites of pain while potentially avoiding adverse effects associated with systemic medications. Opioids, prescription nonsteroidal anti-inflammatory drugs, and over-the-counter oral medications are associated with systemic toxicities, increasing morbidity and mortality. This study evaluated a topical analgesic pain-relieving patch in reducing pain severity and improving function in patients with mild to moderate arthritic, neurological, or musculoskeletal pain. PATIENTS AND METHODS: This Institutional Review Board-approved study evaluated the effectiveness of a topical pain-relieving patch in reducing Brief Pain Inventory (BPI) scores in patients. The treatment group (TG) (n=152) received patches for 14 days. A control group (CG) (n=47) did not receive the patch. After day 14, 34 CG patients crossed over to treatment (CROSSG) with the patch. Surveys were administered to patients at baseline and 14 days to assess changes in pain severity and interference. Changes in oral pain medication use, side effects, and satisfaction use were also assessed. RESULTS: Paired data were collected in the CG, TG and CROSSG. At day 14, TG pain severity score and pain interference score decreased (49% and 58.1%, respectively). Pain severity and interference scores decreased less in the CG (12.3% and 14.8%, respectively). In the study, 60.5% of the TG were using concomitant oral pain medications "a lot less", and 90.8% were very/extremely satisfied with the patch. CROSSG patients showed similar reductions in pain severity and interference scores after patch treatment. No side effects of treatment were reported. CONCLUSION: Results indicate that this topical analgesic pain-relieving patch can reduce BPI pain severity and interference scores in adult patients with mild to moderate arthritic, neurological, and musculoskeletal pain and should be considered as a treatment option.