-
Cureus Aug 2022Rhabdomyolysis secondary to prescription drug-drug interactions can be an overlooked life-threatening emergency. Amphetamines and similar substances have been...
Rhabdomyolysis secondary to prescription drug-drug interactions can be an overlooked life-threatening emergency. Amphetamines and similar substances have been associated with muscle lysis secondary to increased sympathetic activity that can cause myotoxicity, hyperthermia, and increased muscular activity. Anabolic steroids may also be a predisposing factor in developing rhabdomyolysis. A high index of suspicion for drug-induced rhabdomyolysis in a patient presenting with atraumatic extremity pain can facilitate rapid diagnosis and treatment. We present a case of drug-induced rhabdomyolysis likely secondary to a previously unreported medication interaction.
PubMed: 36134084
DOI: 10.7759/cureus.27988 -
Cureus Jun 2022Hippocampal ischemia is a rare complication of cocaine abuse that has been thought to arise from vasospasm, anoxic injury, and/or catecholaminergic excitotoxicity. We...
Hippocampal ischemia is a rare complication of cocaine abuse that has been thought to arise from vasospasm, anoxic injury, and/or catecholaminergic excitotoxicity. We present two cases of patients abusing cocaine, who presented with an acute onset anterograde amnesia due to bilateral hippocampal ischemia, and had different outcomes. Case 1 is a 49-year-old male with a history of IV heroin abuse who presented after being found down for an unknown period of time. He awoke with no memory of events leading up to hospitalization and was unable to retain new information. Urine toxicology was positive for cocaine and opiates. Traditional vascular risk factors included obesity, hypertension, and hyperlipidemia. His recovery was complicated by continued drug use and one episode of cardiac arrest. Despite cognitive rehabilitation, only minimal improvements in his anterograde memory were observed during his annual follow-up. Case 2 is a 23-year-old male with a history of attention deficit disorder treated with dexmethylphenidate and a history of consistent marijuana and cocaine abuse, who presented with nausea, vomiting, chest pain, shortness of breath, and acute-onset short-term memory loss. Urine toxicology was negative for cocaine and opiates and positive for marijuana. He had no known vascular risk factors. With cognitive rehabilitation and discontinuation of illicit drug use, he demonstrated a significant improvement in his memory function over the course of six months. Brain MRI in both patients showed symmetric bilateral hippocampal diffusion restriction without post-contrast enhancement with corresponding hyperintensities on fluid-attenuated inversion recovery sequences. In both patients, cerebrospinal fluid (CSF) studies were unremarkable for inflammation or infection, and electroencephalograms were normal in awake and drowsy states. Bilateral hippocampal ischemia should be considered as a potential cause of acute onset anterograde amnesia in patients with a history of cocaine abuse. Other substances such as heroin and dexmethylphenidate may potentially increase susceptibility for hippocampal ischemia in patients using cocaine. Discontinuation of illicit drug abuse can influence the degree of recovery from acute bilateral hippocampal ischemia.
PubMed: 35915690
DOI: 10.7759/cureus.26435 -
Journal of Child and Adolescent... Jun 2022The study was designed to determine (1) the pharmacokinetic (PK) profile of dexmethylphenidate (d-MPH) after oral administration of three dosage strengths of a new...
Dose Proportionality and Steady-State Pharmacokinetics of Serdexmethylphenidate/Dexmethylphenidate, a Novel Prodrug Combination to Treat Attention-Deficit/Hyperactivity Disorder.
The study was designed to determine (1) the pharmacokinetic (PK) profile of dexmethylphenidate (d-MPH) after oral administration of three dosage strengths of a new treatment containing d-MPH and a novel prodrug, serdexmethylphenidate (SDX); (2) the dose proportionality of the different SDX/d-MPH dosages; and (3) the steady-state PK profile of d-MPH and SDX after multiple dosing of SDX/d-MPH. Twenty-three healthy volunteers (aged 18-55 years) under fasted conditions received in a crossover design SDX/d-MPH 26.1/5.2 mg (Treatment A), 39.2/7.8 mg (Treatment B), and 52.3/10.4 mg (Treatment C) for a total d-MPH hydrochloride equivalent dose of 20, 30, and 40 mg, respectively. After a 96-hour washout period, all participants received four consecutive daily doses of SDX/d-MPH 52.3/10.4 mg. Blood samples were collected for measurement of plasma d-MPH and SDX and for PK analysis. Administration of all three doses of SDX/d-MPH resulted in a rapid rise and slow decline in the plasma concentration of d-MPH. For Treatments A, B, and C, mean (± standard deviation) maximum concentrations () were 7.1 ± 2.1, 9.8 ± 2.8, and 13.8 ± 3.8 ng/mL, and overall exposures (AUC) were 97.2 ± 28.8, 142.5 ± 41.2, and 199.8 ± 57.2 h*ng/mL, respectively. Dose-normalized , AUC, and AUC for d-MPH were similar when comparing the high and low doses versus the middle dose. Power model regression analysis revealed that and AUC proportionally increased with an increase in SDX/d-MPH dose. In the multiple-dose study, d-MPH reached steady state before the third dose, and SDX after the first dose. The PK profile of SDX/d-MPH is characterized by a rapid rise and a gradual decline in d-MPH concentration, with proportional and AUC across doses. The PK attributes of SDX/d-MPH may optimize symptom control from early morning to early evening, while the demonstrated dose proportionality may facilitate initial dose titration and ongoing dose adjustment.
Topics: Area Under Curve; Attention Deficit Disorder with Hyperactivity; Biological Availability; Central Nervous System Stimulants; Cross-Over Studies; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate; Prodrugs
PubMed: 35666231
DOI: 10.1089/cap.2022.0015 -
JCO Oncology Practice Feb 2022The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms. (Review)
Review
PURPOSE
The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms.
METHODS
We reviewed relevant guidelines and compiled drugs used to manage seven cancer-associated symptoms (anorexia and cachexia, chemotherapy-induced peripheral neuropathy, constipation, diarrhea, exocrine pancreatic insufficiency, cancer-associated fatigue, and chemotherapy-induced nausea and vomiting). Using GoodRx website, we identified the retail price (cash price at retail pharmacies) and lowest price (discounted, best-case scenario of out-of-pocket costs) for patients without insurance for each drug or formulation for a typical fill. We describe lowest prices here.
RESULTS
For anorexia and cachexia, costs ranged from $5 US dollars (USD; generic olanzapine or mirtazapine tablets) to $1,156 USD (brand-name dronabinol solution) and varied widely by formulation of the same drug or dosage: for olanzapine 5 mg, $5 USD (generic tablet) to $239 USD (brand-name orally disintegrating tablet). For chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 USD (generic) to $529 USD (brand-name). For constipation, the cost of sennosides or polyethylene glycol was <$15 USD, whereas newer agents such as methylnaltrexone were expensive ($1,001 USD). For diarrhea, the cost of generic loperamide or diphenoxylate-atropine tablets was <$15 USD. For exocrine pancreatic insufficiency, only brand-name formulations were available, range of cost, $1,072 USD-$1,514 USD. For cancer-associated fatigue, the cost of generic dexamethasone or dexmethylphenidate was <$15 USD, whereas brand-name modafinil was more costly ($1,284 USD). For a 4-drug nausea and vomiting prophylaxis regimen, costs ranged from $181 USD to $1,430 USD.
CONCLUSION
We highlight the high costs of many symptom control drugs and the wide variation in the costs of these drugs. These findings can guide patient-clinician discussions about cost-effectively managing symptoms, while promoting the use of less expensive formulations when possible.
Topics: Antineoplastic Agents; Drug Costs; Drugs, Generic; Financial Stress; Humans; Neoplasms; Pharmacies
PubMed: 34558297
DOI: 10.1200/OP.21.00466 -
Ochsner Journal 2021Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of...
Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of an association between attention-deficit/hyperactivity disorder (ADHD) stimulant medication (ASM) and various types of alopecia. We conducted a retrospective case-control medical record review of patients between the ages of 6 and 18 years seen in dermatology clinics during a 10-year period. Cases included patients diagnosed with alopecia areata (AA), alopecia totalis (AT), or alopecia universalis (AU). We matched 3 controls on age and sex to each case. We reviewed patients' medical records for the following medications: lisdexamfetamine, amphetamine/dextroamphetamine, dexmethylphenidate, and methylphenidate. We examined the association between medications used to treat ADHD and diagnoses of AA, AT, and/or AU by calculating a series of odds ratios and 95% CIs. We identified 124 cases (110 with AA, 11 with AT, and 3 with AU) and 372 controls. We found a strong association between AU and ASM use (<0.0071). No relationship between ASM use and other types of hair loss was found. Although the sample size of cases with AU was small, we found a significant association between AU and ASM. While further study is needed, practitioners may consider close monitoring of patients with AA who use ASM for the development of worsening disease and discontinue the medication if the patient experiences an increase in hair loss that appears to be progressing to AU.
PubMed: 34239372
DOI: 10.31486/toj.20.0025 -
JAMA Pediatrics Sep 2021Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms...
IMPORTANCE
Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation.
OBJECTIVE
To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis.
EXPOSURES
Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
MAIN OUTCOMES AND MEASURES
Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population.
RESULTS
Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%).
CONCLUSIONS AND RELEVANCE
This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bupropion; Child; Child, Preschool; Cohort Studies; Comorbidity; Data Mining; Depressive Disorder, Major; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Female; Health Services Accessibility; Humans; Insurance; Lisdexamfetamine Dimesylate; Male; Managed Care Programs; Prevalence; Retrospective Studies
PubMed: 34097007
DOI: 10.1001/jamapediatrics.2021.1329 -
PloS One 2021Patient access and adherence to chronic medications is critical. In this work, we evaluate whether disruptions related to Covid-19 have affected new and existing...
Patient access and adherence to chronic medications is critical. In this work, we evaluate whether disruptions related to Covid-19 have affected new and existing patients' access to pharmacological therapies without interruption. We do so by performing a retrospective analysis on a dataset of 9.4 billion US prescription drug claims from 252 million patients from May, 2019 through August, 2020 (about 93% of prescriptions dispensed within those months). Using fixed effect (conditional likelihood) linear models, we evaluate continuity of care, how many days of supply patients received, and the likelihood of discontinuing therapy for drugs from classes with significant population health impacts. Findings indicate that more prescriptions were filled in March 2020 than in any prior month, followed by a significant drop in monthly dispensing. Compared to the pre-Covid era, a patient's likelihood of discontinuing some medications increased after the spread of Covid: norgestrel-ethinyl estradiol (hormonal contraceptive) discontinuation increased 0.62% (95% CI: 0.59% to 0.65%, p<0.001); dexmethylphenidate HCL (ADHD stimulant treatment) discontinuation increased 2.84% (95% CI: 2.79% to 2.89%, p<0.001); escitalopram oxalate (SSRI antidepressant) discontinuation increased 0.57% (95% CI: 0.561% to 0.578%, p<0.001); and haloperidol (antipsychotic) discontinuation increased 1.49% (95% CI: 1.41% to 1.57%, p<0.001). In contrast, the likelihood of discontinuing tacrolimus (immunosuppressant) decreased 0.15% (95% CI: 0.12% to 0.19%, p<0.001). The likelihood of discontinuing buprenorphine/naloxone (opioid addiction therapy) decreased 0.59% (95% CI: 0.55% to 0.62% decrease, p<0.001). We also observe a notable decline in new patients accessing these latter two therapies. Most US patients were able to access chronic medications during the early months of Covid-19, but still were more likely to discontinue their therapies than in previous months. Further, fewer than normal new patients started taking medications that may be vital to their care. Providers would do well to inquire about adherence and provide prompt, nonjudgmental, re-initiation of medications. From a policy perspective, opioid management programs seem to demonstrate a robust ability to manage existing patients in spite of disruption.
Topics: Analgesics, Opioid; Antidepressive Agents; Antipsychotic Agents; COVID-19; Central Nervous System Stimulants; Contraceptive Agents, Hormonal; Datasets as Topic; Drug Prescriptions; Humans; Immunosuppressive Agents; Insurance, Pharmaceutical Services; Medication Adherence; Pandemics; Retrospective Studies; United States
PubMed: 33793663
DOI: 10.1371/journal.pone.0249453 -
Clinical Case Reports Mar 2020Dexmethylphenidate, and potentially other methylphenidates used in the treatment of attention deficit hyperactivity disorder (ADHD), may cause severe muscle pain and...
Dexmethylphenidate, and potentially other methylphenidates used in the treatment of attention deficit hyperactivity disorder (ADHD), may cause severe muscle pain and stiffness. Medication side effects should be considered as the possible cause if a patient with ADHD develops severe symptoms.
PubMed: 32185027
DOI: 10.1002/ccr3.2628 -
Harm Reduction Journal Oct 2017As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing... (Review)
Review
As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing prohibitionist policies to reduce consumption, and ambiguity in literature towards best practices to address this population, we present a literature review that seeks effective solutions educational institutions can apply to improve outcomes for students who use drugs. Motivations for use, effects of the substances, an analysis of efforts to control use from educational institutions, and suggestions on promoting most effective outcomes based on harm reduction, are described. Theory, quantitative, and qualitative works from systematic reviews, cohort studies, and epidemiological assessments are examined on the "study drugs" methylphenidate, dextroamphetamine, and amphetamine, also known as Adderall, Ritalin, Focalin, and Concerta. There is a focus on postsecondary students ages 18-25 in North America. Results show important risk factors for drug use including low perceived self-efficacy or enjoyment in courses, poor accommodation of special needs, reliance on external validation, having a low GPA, and experiencing a mental health issue. There is much misconception on the health and academic effects of these drugs in literature, among students, and on online knowledge sources. We suggest these drugs do not improve GPA and learning, while they might temporarily increase memory, but with detrimental negative health effects. Campaigns that address underlying factors of use can be most successful in mitigating harms.
Topics: Academic Success; Adolescent; Adult; Amphetamines; Central Nervous System Stimulants; Dexmethylphenidate Hydrochloride; Female; Harm Reduction; Humans; Male; Methylphenidate; Motivation; Prescription Drug Misuse; Risk Factors; Students; Substance-Related Disorders; Young Adult
PubMed: 28985738
DOI: 10.1186/s12954-017-0194-6 -
Journal of Clinical Psychopharmacology Aug 2017Ethanol coadministered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/PURPOSE
Ethanol coadministered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects. We asked the question: Are these ethanol-MPH interactions based more fundamentally on (1) inhibition of postabsorption d-MPH metabolism or (2) acceleration of MPH formulation gastric dissolution by ethanol in the stomach? This was investigated using the pulsatile, distinctly biphasic, spheroidal oral drug absorption systems of dl-MPH and d-MPH.
METHODS
In a randomized, 4-way crossover study, 14 healthy subjects received pulsatile dl-MPH (40 mg) or d-MPH (20 mg), with or without ethanol (0.6 g/kg), dosed 4 hours later. These 4 hours allowed the delayed-release second MPH pulse to reach a more distal region of the gut to preclude gastric biopharmaceutical influences. Plasma was analyzed using a highly sensitive chiral method. Subjective/physiological effects were recorded.
FINDINGS/RESULTS
Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01) and the partial area under the plasma concentration curve from 4 to 8 hours by 25% (P < 0.05). The respective values for enantiopure d-MPH were 27% (P = 0.001) and 20% (P < 0.01). The carboxylesterase 1-mediated transesterification metabolite ethylphenidate served as a biomarker for coexposure. Ethanol significantly potentiated stimulant responses to either formulation.
IMPLICATIONS/CONCLUSIONS
These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations. Understanding the pharmacology underlying the frequent coabuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid attention-deficit/hyperactivity disorder-alcohol use disorder.
Topics: Administration, Oral; Adult; Biological Availability; Central Nervous System Stimulants; Cross-Over Studies; Dexmethylphenidate Hydrochloride; Drug Interactions; Ethanol; Female; Healthy Volunteers; Humans; Male; Methylphenidate; Young Adult
PubMed: 28590363
DOI: 10.1097/JCP.0000000000000721