buprenorphine and Drug-Related-Side-Effects-and-Adverse-Reactions

Topics: Aged; Analgesics, Opioid; Buprenorphine; Drug-Related Side Effects and Adverse Reactions; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Topics: Administration, Sublingual; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

In a recent publication by Putman et al. (2003), salmeterol, morphine/methadone and buprenorphine were quoted as examples of pharmaceutical drugs whose immunotoxicity has only been revealed by conduct of specific immune function tests in non-clinical studies. Review of the published non-clinical data for these drugs has shown that there is no clear evidence of immunotoxicity of salmeterol in these studies, and in addition, there are no clinical issues regarding adverse immunological effects of this drug. Of the opioid drugs, only very minor evidence of immunosuppression by morphine, and marginal evidence of slight immunostimulation by buprenorphine were detected in the non-clinical immune function assays performed at high doses. Methadone showed no effects on immune function assays in animals. As some immunomodulation by opioid drugs might have been expected based on the known pharmacological properties of this drug class, the marginal effects, or lack of effects observed in the immune function tests does raise a question about the sensitivity and specificity of the assays to detect clinically relevant changes. This review has suggested that, based on the cited examples, there is no strong case for routine non-clinical immune function testing of all new pharmaceutical products. A more rigorous evaluation of non-clinical immune function tests, and their ability to discriminate between clinically relevant and non-clinically relevant immunosuppression, is needed before definitive regulatory guidance in this area can be finalized.

Topics: Adrenergic beta-Agonists; Albuterol; Animals; Buprenorphine; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Guidelines as Topic; Humans; Immune System Diseases; Immunity; Methadone; Morphine; Narcotics; Salmeterol Xinafoate

Attention-deficit and hyperactivity disorder (ADHD) is frequently diagnosed in patients with substance use disorders (SUDs), including opioids. There remains concern about the safety and efficacy of prescription amphetamines (PAs) and their impact on effectiveness of opioid use disorder (OUD) treatment with buprenorphine.. To assess the effect of PAs on OUD buprenorphine treatment retention and/or SUD-related emergency admission or drug-related poisonings.. We used a retrospective cohort design with a secondary analysis of data from Merative MarketScan Commercial and Multi-State Medicaid Databases from 1 January 2006 to 31 December 2016. Individuals included were aged 12-64 years, had an OUD diagnosis and were prescribed buprenorphine. Our analysis used multivariable Cox regression to evaluate the relationship between PA receipt and time to buprenorphine discontinuation. The second part focused on subsamples of buprenorphine initiators who had either (1) any SUD-related emergency admissions or (2) drug-related poisoning. These outcomes were modelled as a function of PA exposure using conditional logistic regression models as part of a within-person, case-crossover design.. Our sample had 90 269 patients with OUD (mean age 34.2 years (SD=11.3)) who initiated buprenorphine. Being prescribed a PA was associated with improved buprenorphine retention among individuals both with (adjusted HR (aHR) 0.91 (95% CI 0.86 to 0.97)) and without a concurrent psychostimulant use disorder (PSUD) (aHR 0.92 (95% CI 0.90 to 0.93)).. PA use was associated with improved buprenorphine retention in people with OUD with and without co-occurring PSUD. The risks of acute SUD-related events and drug-related poisonings associated with PA use did not differ when comparing PA-using days with days without PA use.. Patients with OUD on buprenorphine should receive treatment with a PA when indicated.

Topics: Adult; Amphetamines; Buprenorphine; Cross-Over Studies; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence.. To assess the purpose and associated risks of off-label gabapentin use in OUD treatment.. This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day.. Days covered by filled gabapentin prescriptions.. Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.. A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage.. Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Female; Gabapentin; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; United States

Buprenorphine is a semi-synthetic opioid used in the treatment of opioid dependence and chronic pain. The current study aimed to determine the characteristics and circumstances of all recorded cases of buprenorphine-related toxicity death in Australia; determine toxicology and organ pathology; and compare these profiles to cases of death due to buprenorphine-related traumatic injury.. All cases of buprenorphine-related drug toxicity death were retrieved from the National Coronial Information System (2000-2019), as were all cases of buprenorphine-related traumatic injury. Information was collected on cause of death, case characteristics, toxicology and major organ pathology.. A total of 314 cases of drug toxicity and 55 of traumatic injury were identified. Toxicity cases were significantly older (40.5 v 36.1 years), more likely to have a history of chronic pain (OR 2.95), less likely to have a history of injecting drug use (OR 0.09), but more likely to have injected buprenorphine proximal to death (OR 4.90). There were no group differences in buprenorphine or norbuprenorphine toxicology. Toxicity cases were more likely to have hypnosedatives (OR 2.08) and other opioids (OR 4.69) present, but less likely to have psychostimulants (OR 0.26) and THC (OR 0.45). Toxicity cases were more likely to be obese (OR 4.05), have pre-existing cardiovascular disease (OR 4.02) and heavier hearts (412.1 v 355.2 g).. Buprenorphine-related toxicity death cases differed from trauma deaths in their characteristics, toxicology and disease. Fatal buprenorphine toxicity is associated with older age, concurrent use of depressants and cardiovascular disease.

Topics: Adult; Aged; Analgesics, Opioid; Australia; Buprenorphine; Cause of Death; Central Nervous System Stimulants; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Opiate Overdose; Opioid-Related Disorders

Topics: Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Child; Drug-Related Side Effects and Adverse Reactions; Humans; Poisons; United States

Buprenorphine is a highly effective medication treatment for opioid use disorder (OUD) that can be prescribed in multiple treatment settings. Treatment retention, however, remains a challenge. In this study, we examined the association of days of supply as well as daily dosage of the initial buprenorphine prescription with treatment discontinuation and adverse opioid-related events following buprenorphine initiation.. 2011 to 2015 Health Care Cost Institute commercial claims data were analyzed for individuals aged 18-64 years initiating buprenorphine treatment (N = 17,158). Treatment discontinuation was defined as a gap of 30 days or more in buprenorphine use within 180 days of initiation. Adverse opioid-related events were defined as having at least one emergency department visit or inpatient admission involving opioid poisoning, dependence or abuse within 360 days of initiation. We conducted multivariate logistic regressions to estimate adjusted odds ratios of outcomes associated with daily dose (≤4 mg vs. >4 mg) and days of supply (≤7, 8-15, 16-27, or ≥ 28 days) of the initial buprenorphine prescription.. Over one-half (55%) of individuals discontinued buprenorphine within 180 days and 13% experienced at least one adverse opioid-related event within 360 days of initiation. Both a lower initial dose [≤4 mg, OR = 1.79, p < 0.01] and fewer initial days of supply [≤7 days vs. ≥28 days, OR = 1.32, p < 0.01] [8-15 days vs. ≥28 days, OR = 1.22, p < 0.01] were associated with increased odds of discontinuation. While a lower initial dose was not associated with adverse events, fewer initial days of supply were associated with a higher risk of adverse events, even after controlling for treatment discontinuation.. In this population of commercially insured, non-elderly adults, we found that fewer initial days of supply as well as a lower initial dose were associated with increased likelihood of treatment discontinuation, highlighting the importance of prescribing decisions when initiating buprenorphine for OUD.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Insurance Claim Review; Male; Medication Adherence; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; United States; Young Adult

Opioid substitution treatment (OST) is often continued long-term and, therefore, opioid-associated symptoms are of interest. Symptoms associated with methadone maintenance treatment (MMT) in men are well described, but there are fewer reports concerning symptoms associated with buprenorphine maintenance treatment (BMT) and very few reports among women.. Recipients of BMT (n=113) and MMT (n=184), non-opioid users (n=105) and opioid users not receiving OST (n=87) completed the Patient Assessment of Constipation (PAC-SYM) and a general symptom checklist. Multivariate analysis included other potential moderators of opioid-associated symptoms.. Opioid users reported a higher frequency and severity of symptoms than non-opioid users. Constipation, dry mouth, decreased appetite, sweating and fatigue were highly prevalent in the previous 30days (51-80%). Nausea, itchy skin, trouble urinating, menstrual problems, lightheadedness, blurred vision, heart racing were also common (30-50%). Non-OST opioid users had significantly higher frequency and severity than OST recipients of nausea, vomiting, diarrhoea, decreased appetite, sweating and itchy skin. Sweating was significantly more common in MMT than BMT. Constipation scores were higher in women, otherwise most sex differences were small. Higher PAC-SYM scores were associated with vomiting (OR=1.04) and sweating (OR=1.06). Cannabis use was associated with vomiting (OR=2.19). Constipation (OR=1.07), insomnia (OR=2.5) and depression (OR=2.82) were associated with fatigue.. Men and women receiving OST report similarly high rates of somatic symptoms, though less than opioid users not receiving OST. There were few differences between BMT and MMT. Buprenorphine might be preferred where sweating is problematic. Several modifiable factors were identified.

Topics: Adult; Analgesics, Opioid; Australia; Buprenorphine; Case-Control Studies; Constipation; Depression; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Sex Factors; Young Adult

To study drug safety and the reporting behavior of adverse drug reactions (ADR) related to agents used for opioid replacement therapy (ORT) we conducted a cross-sectional questionnaire-based telephone survey among physicians who provide outpatient ORT in Germany (n=176; response rate=55.7%). Most respondents (n=97/55.1%) reported that they observe ADR related to buprenorphine, (dihydro)codeine, and (levo)methdone rarely (n=38/21.6%), very rarely (n=39/22.2%) or never (n=20/11.4%). Methadone was reported to be most frequently associated with the occurrence of ADR (n=82/46.6%), followed by levomethadone (n=33/18.8%), buprenorphine (n=6/3.4%), and dihydrocodeine (n=3/1.7%). Frequently observed ADR related to these agents were gastrointestinal, nervous system/psychiatric disorders, and hyperhidrosis. Methadone and levomethadone (not buprenorphine) were frequently associated with fatigue, weight gain, and sexual dysfunction. Hundred twenty nine participants (73.3%) stated that they never report ADR related to ORT; n=19 (10.8%) did so when referring to ADR related to their complete medical practice (X

Topics: Analgesics, Opioid; Buprenorphine; Drug-Related Side Effects and Adverse Reactions; Female; Germany; Health Care Surveys; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Physicians

Despite the critical need, no previous research has substantiated safe opioid analgesics without abuse liability in primates. Recent advances in medicinal chemistry have led to the development of ligands with mixed mu opioid peptide (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor agonist activity to achieve this objective. BU08028 is a novel orvinol analog that displays a similar binding profile to buprenorphine with improved affinity and efficacy at NOP receptors. The aim of this preclinical study was to establish the functional profile of BU08028 in monkeys using clinically used MOP receptor agonists for side-by-side comparisons in various well-honed behavioral and physiological assays. Systemic BU08028 (0.001-0.01 mg/kg) produced potent long-lasting (i.e., >24 h) antinociceptive and antiallodynic effects, which were blocked by MOP or NOP receptor antagonists. More importantly, the reinforcing strength of BU08028 was significantly lower than that of cocaine, remifentanil, or buprenorphine in monkeys responding under a progressive-ratio schedule of drug self-administration. Unlike MOP receptor agonists, BU08028 at antinociceptive doses and ∼10- to 30-fold higher doses did not cause respiratory depression or cardiovascular adverse events as measured by telemetry devices. After repeated administration, the monkeys developed acute physical dependence on morphine, as manifested by precipitated withdrawal signs, such as increased respiratory rate, heart rate, and blood pressure. In contrast, monkeys did not show physical dependence on BU08028. These in vivo findings in primates not only document the efficacy and tolerability profile of bifunctional MOP/NOP receptor agonists, but also provide a means of translating such ligands into therapies as safe and potentially abuse-free opioid analgesics.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cocaine; Drug-Related Side Effects and Adverse Reactions; Humans; Ligands; Opioid Peptides; Pain; Primates; Receptors, Opioid, mu; Respiratory Insufficiency

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but increasingly described phenomenon of immune activation and organ dysfunction in association with a wide variety of medications. This reaction shows a broad spectrum of clinical presentation and severity, ranging from mild to lethal. Treatment strategies of immune suppression appear be helpful in some cases, but treatment failures occur frequently with reported mortality rates of 5% to 10%. We present a pediatric case of DRESS syndrome associated with either lamotrigine or bupropion, leading to multiorgan involvement and life-threatening complications of respiratory failure and cardiac arrest. After failing to improve with removal of these medications and administration of systemic corticosteroids, our patient showed dramatic, sustained clinical response to therapeutic plasma exchange. To our knowledge, this is the first reported case of therapeutic plasma exchange used for life-threatening DRESS syndrome in a pediatric patient. This case suggests needed research for this therapeutic option in life-threatening DRESS syndrome resistant to high-dose steroids.

Topics: Adolescent; Buprenorphine; Disease Management; Drug-Related Side Effects and Adverse Reactions; Eosinophilia; Female; Humans; Lamotrigine; Plasma Exchange; Pseudolymphoma; Severity of Illness Index; Triazines

Buprenorphine is considered to have little respiratory side effects at therapeutic doses and the partial agonistic properties should produce a "ceiling effect" for respiratory depression at higher doses. Still, there are several reports on buprenorphine related deaths. Most deaths involve drug users and the co-administration of other CNS depressant drugs as well as reduced tolerance have been suggested to be risk factors. The primary aims were to investigate if lack of tolerance and/or co-ingestion of other psychotropic drugs are significant risk factors in buprenorphine fatalities. From July 2005 to September 2009, all autopsy cases where buprenorphine or norbuprenorphine had been detected in femoral blood and where analysis of buprenorphine had been performed in urine were selected. Results from the postmortem examination and toxicology were compiled. Postmortem toxicology was performed using the routine methodology at the laboratory. In total, 97 subjects were included in the study. These were divided into four groups; Intoxication with buprenorphine (N=41), Possible intoxication with buprenorphine (N=24), Control cases where buprenorphine was not the cause of death (N=14), and Unclear (N=18). The metabolite to parent compound ratios in both blood and urine in the Intoxication group were significantly different from those in the Control and Unclear groups. An extensive poly-drug use was seen in all groups with several additional opioids in the Possible group (54%) and in the Unclear group (78%) and hypnotics or sedatives in more than 75% of the Intoxication, Possible, and Unclear cases. Illicit drugs were present in all groups but not to a great extent with amphetamine and tetrahydrocannabinol as the main findings. Interestingly, 4 cases in the Intoxication group presented with no other significant drugs in blood other than buprenorphine. We conclude that a lethal concentration of buprenorphine in blood cannot be defined. Instead the analysis of blood as well as urine can be an important tool to show that the drug was taken shortly before death and to rule out a continuous use of buprenorphine supporting the notion that abstinence is an important risk factor. The presence of alprazolam in more than 40% of the Intoxications and the presence of hypnotics and sedatives in 75% of the Intoxications suggests that these drugs interact with buprenorphine producing toxic effects that buprenorphine alone would not have produced. Still, in 10% of the Intoxication

Topics: Adult; Buprenorphine; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Female; Forensic Pathology; Forensic Toxicology; Humans; Hypnotics and Sedatives; Illicit Drugs; Lung; Male; Middle Aged; Narcotics; Pharmaceutical Preparations; Prescription Drug Misuse; Pulmonary Edema; Respiration; Retrospective Studies; Risk Factors; Substance-Related Disorders; Young Adult