Extended-release Capsules Research Articles

PND3 - Budget Impact Analysis of Extended-Release Phenytoin Capsule (Original) Compared With Immediate-Release Phenytoin Capsule (Generic) for Epilepsy Patients in Thailand

PND3 - Budget Impact Analysis of Extended-Release Phenytoin Capsule (Original) Compared With Immediate-Release Phenytoin Capsule (Generic) for Epilepsy Patients in Thailand

Pharmacokinetic/Pharmacodynamic Correlation Analysis of Amantadine for Levodopa-Induced Dyskinesia.

Dyskinesia is a common motor complication associated with the use of levodopa to treat Parkinson's disease. Numerous animal studies in mice, rats, and nonhuman primates have demonstrated that the N-methyl-d-aspartate antagonist, amantadine, dose dependently reduces levodopa-induced dyskinesia (LID). However, none of these studies characterized the amantadine plasma concentrations required for a therapeutic effect. This study evaluates the pharmacokinetic (PK)/pharmacodynamic (PD) relationship between amantadine plasma concentrations and antidyskinetic efficacy across multiple species to define optimal therapeutic dosing. The PK profile of amantadine was determined in mice, rats, and macaques. Efficacy data from the 6-hydroxydopamine rat and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine macaque model of LID, along with previously published antidyskinetic efficacy data, were used to establish species-specific PK/PD relationships using a direct-effect maximum possible effect model. Results from the PK/PD model were compared with amantadine plasma concentrations and antidyskinetic effect in a phase 2 study in patients with Parkinson's disease treated with ADS-5102, an extended-release amantadine capsule formulation. Outcomes from each of the species evaluated indicate that the EC50 of amantadine for reducing dyskinesia range from 1025 to 1633 ng/ml (1367 ng/ml for an all-species model). These data are consistent with the mean amantadine plasma concentrations observed in patients with Parkinson's disease (∼1500 ng/ml) treated with ADS-5102 at doses that demonstrated a statistically significant reduction in dyskinesia. These results demonstrate that the EC50 of amantadine for reducing dyskinesia is consistent across multiple species and supports a plasma concentration target of ∼1400 ng/ml to achieve therapeutic efficacy.

Med Check

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessMed CheckNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:3 Aug 2018https://doi.org/10.1176/appi.pn.2018.8a3FDA Panel Rejects Abuse-Deterrent Oxycodone FormulationParticipants in a joint meeting of the Food and Drug Administration’s Anesthetic and Analgesic Drug Products Advisory Committee and its Drug Safety and Risk Management Advisory Committee in June voted 14-3 not to recommend the approval of Remoxy ER (oxydone extended-release capsules) for the management of severe pain. Remoxy ER, made by Pain Therapeutics Inc., is a high-viscosity gel formulation designed to keep people from being able to cut, grate, or inject the drug. Some committee members suggested that data presented on the efficacy, safety, and risk-benefit profile of Remoxy ER did not support approval of its application, especially regarding claims of abuse deterrence.Sage Announces Expedited Development Plan for Depression MedicationSage Therapeutics in June announced its expedited development plan for its lead compound SAGE-217 following a meeting with the FDA. SAGE-217, a drug that targets the GABA-A receptor, received FDA breakthrough status in February for the treatment of major depressive disorder (MDD).The new plan includes expedited approval pathways for SAGE-217 for both MDD and postpartum depression (PPD). An ongoing phase 2 study comparing depressive symptoms in women with PPD who receive either 30 mg SAGE-217 or placebo for two weeks was confirmed as appropriate to support registration for PPD, the company noted. The FDA also requested n additional phase 3 trial for MDD. The trial will compare outcomes in 450 patients who take SAGE-217 (20 mg or 30 mg) or placebo for two weeks. Sage will also begin a one-year open-label study of patients with major depression to acquire additional safety data and evaluate the long-term effectiveness of two weeks of SAGE-217 for recurrent major depressive episodes. Saladax Signs Agreement to License Blood Tests For Antipsychotic LevelsIn June, the diagnostics company Saladax Biomedical Inc. signed a license agreement with Janssen Pharmaceutical NV—one of the Janssen Pharmaceutical companies—to acquire exclusive patent rights for diagnostic blood tests that can determine drug levels in patients undergoing treatment with antipsychotic medications. “This intellectual property, along with the existing patents that Saladax already owns, places Saladax in a predominant position in the field of antipsychotic drug testing,” according to a press release by the company. Saladax in March received approval to sell two of its diagnostic tests on the European market: the MyCare Total Risperidone Assay Kit and MyCare Paliperidone Assay Kit. The company has four additional tests for aripiprazole, clozapine, olanzapine, and quetiapine that it expects will receive European clearance later this year. Saladax stated the company will soon seek FDA clearance for these tests as well. Guidelines Released For Use of Ketamine to Treat Acute PainThe American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine, and American Society of Anesthesiologists recently joined together to develop consensus guidelines on the use of intravenous ketamine to treat both chronic and acute pain.These guidelines, published in the journal Regional Anesthesia and Pain Medicine in June, cover a range of scenarios, but broadly state that moderate evidence supports the use of ketamine for acute pain management following painful surgeries, including in people who are opioid dependent. There is also moderate evidence that ketamine works for chronic spinal pain and complex regional pain syndrome. There is limited evidence to support ketamine for other types of chronic or acute pain. The guidelines noted that ketamine should be avoided in people with poorly controlled cardiovascular disease, those with active psychosis, and pregnant women. ■Schwenk, ES et al. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):456-466. ISSUES NewArchived

Amantadine Extended-Release (GOCOVRI™): A Review in Levodopa-Induced Dyskinesia in Parkinson’s Disease

Amantadine extended-release (ER) capsules (GOCOVRI™) are approved in the USA for the treatment of dyskinesia in patients with Parkinson's disease (PD) receiving levodopa-based therapy, with or without concomitant dopaminergic medications. With a recommended dosage of 274mg once daily at bedtime, this new formulation of amantadine allows a more gradual time to peak plasma amantadine concentration and higher drug concentrations in the morning and throughout the day, the time period when levodopa-induced dyskinesia (LID) is the most problematic. In 13-week (EASE LID3) and 25-week (EASE LID), randomized, double-blind phase III trials, once-daily amantadine ER 274mg capsules significantly improved levodopa-induced dyskinesia (LID), while also increasing ON time without troublesome dyskinesia and reducing OFF time and ON time with troublesome dyskinesia from the morning and throughout the day, compared with placebo. In the ongoing, longer-term EASE LID2 study (with interim results reported for up to 64weeks), patients previously treated with amantadine ER maintained improvements in LID, as per patient-reported Unified Dyskinesia Rating Scale (UDysRS) scoring and ON/OFF times. Amantadine ER was generally well tolerated, with most adverse events (AEs) being transient and mild or moderate in severity. The most common (incidence >15%) treatment-related AEs in the placebo-controlled trials were hallucinations, dizziness, dry mouth and peripheral oedema. While long-term data are needed to establish durability of response and safety, including the completion of the ≈2-year EASE LID2 study, current evidence indicates that amantadine ER is an effective treatment option to consider in the management of LID in PD patients.

Amphetamine extended-release oral suspension (Adzenys ER™) and orally disintegrating tablets (Adzenys XR-ODT®) in attention-deficit hyperactivity disorder: a profile of their use

Amphetamine extended-release oral suspension (Adzenys ER™) and extended-release orally disintegrating tablets (Adzenys XR-ODT®) are easy-to-administer, long-acting, and convenient CNS stimulant options for treating attention-deficit hyperactivity disorder (ADHD) in children aged ≥ 6 years, adolescents, and adults. The bioavailability of d- and l-amphetamine with Adzenys ER™ suspension and XR-ODT® is equivalent to that of a corresponding dose of the reference product [i.e. mixed amphetamine salt extended-release capsules (MAS ER)], which has well-established efficacy, tolerability, and safety profiles. As Adzenys ER™ suspension/XR-ODT® contain both immediate- and extended-release amphetamine particles, plasma concentrations of d- and l-amphetamine increase rapidly, remain relatively stable for several hours, then slowly decline, allowing for once-daily administration. The use of Adzenys ER™ suspension/XR-ODT® may be of particular benefit in individuals who require a rapid onset and prolonged reduction in ADHD symptoms, as well as those who have difficulty swallowing tablets or capsules whole (neither formulation requires swallowing whole tablets/capsules, and both may be taken without regard to food).

Effect of processing parameters and controlled environment storage on the disproportionation and dissolution of extended-release capsule of phenytoin sodium

Phenytoin sodium (PS) is a narrow therapeutic index drug that dictates maintenance of narrow plasma concentration of the drug. This requires a good quality product that meets regulatory specifications throughout shelf-life as well as during the usage period. Quality of the drug product may change if not develop in a scientific fashion which may have ramifications on clinical outcome. The focus of the study was to understand the effect of process variables and storage conditions on the disproportionation and phase transformation of the drug, and dissolution of extended-release capsules of PS. Four formulations were prepared to contain either powder blend or granules of PS with commonly used excipients. The granules were prepared in a high shear mixture by granulating with water, ethanol or mixture thereof. The capsules were stored in pharmacy vials for 4-weeks at 40 °C/75% RH and 30 °C/65% RH. Formulations were characterized by spectroscopies (FTIR, NIR, and chemical imaging), X-ray powder diffraction (XRPD), dissolution and assay. Granules filled capsule did not meet USP dissolution specifications and there was a significant decrease in dissolution on exposure to stability conditions. Dissolution decreased from 77.56 ± 3.83% to 42.34 ± 4.31%, and 63.96 ± 6.12 to 46.53 ± 2.91 in physical mixture and water granulated formulations, respectively, after four weeks exposure at 40 °C/75% RH. Spectroscopic (NIR, FTIR, and chemical imaging) data indicated disproportionation of the drug during the storage period. Moreover, XRPD data explained a decrease in dissolution in the initial granules filled capsules as well as temperature and humidity exposed samples. It indicated the phase transformation of the drug and/or excipients, disproportionation and/or interactions. These changes further accelerated on exposure to stability conditions. In conclusion, our studies indicated the significant effect of process variables and stability conditions on the critical quality attributes of PS extended-release capsule that has the potential impact on the clinical performance of the product.

Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations

BackgroundAmbroxol relieves cough symptoms based on its secretagogue, anti-inflammatory, anti-oxidant, anti-bacterial, anti-viral, immunomodulatory and local anesthetic effects. The present study was designed to explore differential patient profiles and efficacy against acute respiratory symptoms of four formulations registered as over-the-counter medicines.MethodsNine hundred sixty-five pharmacy customers purchasing one of four branded ambroxol formulations (extended release capsules, adult syrup, pediatric syrup and soft pastilles) filled a questionnaire including a patient-adapted version of the Bronchitis Severity Scale, several questions on degree of impairment by acute cough, time to onset of symptom relief and duration of treatment. Data on pediatric syrup users were entered by their parents. Based on the exploratory character of the study, no hypothesis-testing statistical analysis was applied.ResultsUsers of the pediatric syrup and the pastilles reported somewhat less severe baseline symptoms. The patient-adapted Bronchitis Severity Scale proved feasible as a self-administered tool. Among BSS items, ambroxol formulations improved chest pain while coughing to the largest and sputum to smallest degree (− 75% vs. -40%). Reported efficacy was comparable among formulations with minor differences in favor of the pediatric syrup. Time to onset of symptom relief was less than 60 min in more than 90% of patients and occurred prior to known systemic tmax. Time to onset was the parameter with the greatest differences between formulations, being reported fastest with pastilles and pediatric syrup and, as expected, slowest with extended release capsules. All ambroxol formulations were well tolerated.ConclusionsWe conclude that over-the-counter formulations of ambroxol exhibit comparable user profiles and efficacy. Differences in speed of onset of symptom relief may involve not only those in systemic pharmacokinetics but also local anesthetic effects of immediate release formulations. Differences between pediatric and adult syrup may in part reflect reporting bias.

Pharmacokinetics of ADS-5102 (amantadine) Extended Release Capsules Administered Once-Daily at Bedtime for the Treatment of Dyskinesia (P2.043)

Pharmacokinetics of ADS-5102 (amantadine) Extended Release Capsules Administered Once-Daily at Bedtime for the Treatment of Dyskinesia (P2.043)

Author Correction to: Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.

An Online First version of this article was made available online at http://link.springer.com/journal/40263/onlineFirst/page/1 on 12 March 2018. An error was subsequently identified in the article, and the following correction should be noted.

Amantadine extended-release capsules for levodopa-induced dyskinesia in patients with Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in patients with Parkinson’s disease on chronic levodopa therapy. The management of LID is important as dyskinesia can be disabling and impair quality of life. Currently, there are limited treatment options for the medical management of LID. Amantadine extended-release capsules (Gocovri™) is the first medication that received US Food and Drug Administration approval for the treatment of LID. The following is a review of the pharmacodynamics, efficacy and safety profile, and current state of treatment of amantadine for LID.

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open-label ADS-5102.

BackgroundADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility.MethodsIn an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study.ResultsChange in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102.ConclusionThese open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules

Although most extended-release morphine formulations are indicated for use once-daily (q24h) or twice-daily (q12h), KADIAN (morphine sulfate extended-release) capsules, which contain polymer-coated, extended-release morphine sulfate pellets, are indicated for q24h and q12h dosing. This analysis identified factors that might impact decisions to choose q24h or q12h regimens for patients with chronic, nonmalignant pain. Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM. At week 2, investigators could switch to q12h dosing if indicated. For this analysis, demographics, baseline pain features, efficacy outcomes (changes in pain intensity, sleep interference, quality of life [SF-36v2 Health Survey], and Patient and Clinician Global Assessments of Therapy) were compared between patients who remained on q24h regimens and those who switched to q12h. By week 4 (n = 1,042), 56.8 percent of patients reporting were on q24h dosing, and 43.2 percent were dosing q12h. Older patients remained on q24h regimens more frequently than did younger patients. There were no differences in dosing regimen based on sex or race. Mean daily KADIAN doses and baseline pain scores were lower in patients who remained on q24h compared with those who switched to q12h. Patients who switched to q12h had higher pain scores at baseline and week 2 compared with patients who remained on q24h dosing. They demonstrated a smaller degree of change on the other efficacy outcomes than those who remained on q24h dosing at the week 2 visit. However, once switched to q12h, improvements in efficacy measures at week 4 were comparable between the two schedules; Patient and Clinician Global Assessments of Therapy scores also increased compared with previous therapy. Results were significant versus baseline for all outcomes. Adverse event rates were similar for the two groups; the most common adverse events were constipation and nausea. Results demonstrate that KADIAN was effective in relieving pain and improving sleep and quality-of-life scores, regardless of whether patients dosed q24h or q12h, and that dosing decisions can be made, based on individual factors, within the first few weeks of therapy.

Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial

Background: Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS). Objective: Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment. Methods: This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed. Results: A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE—suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test (p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed. Conclusion: ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.

Bioequivalence of Two Oral Dimethyl Fumarate Extended Release Capsules in Healthy Subjects: A Randomized, Open Label, Single-Dose, 2-Way Crossover Study

The hypothesis for the design of this project was that the extended release formulation containing dimethyl fumarate 240 mg DIMEFUL®, developed by Gador will present similar bioavailability with respect to the reference formulation, TECFIDERA® by Biogen Idec, measured in terms of speed and absorption. A clinical study of single-dose bioequivalence (in 2 stages) was designed to be carried out in healthy subjects. This study was opened of two periods, two sequences, crossed, randomized under fasting conditions. Eight out of ten subjects involved in this pilot study (stage 1) were randomized and completed the 2 periods of administration of the treatments. Data of all the subjects who completed the 2 periods of treatment administration were used for pharmacokinetic purposes. The design of the study was adequate to determine the bioequivalence of the Test and Reference Products. The 7- day washout period was sufficient to allow the complete elimination of the formulations before the next dosing period. Conclusion: In relation to monomethyl fumarate; The extended release formulation containing dimethyl fumarate 240 mg, developed by Gador, DIMEFUL®, presents similar bioavailability, measured in terms of speed and extension of absorption in relation to the reference formulation, TECFIDERA® by Biogen Idec. Intrasubject CVs were on the order of 30% to 40% for the 3 pharmacokinetic parameters; indicating that the molecule and/or the formulation shows high variability in absorption and must be considered for the calculation of sample size of Stage 2. This improved process will serve for clinical assessment in patients. Individual plasma concentrations showed results lower than the lower limit of quantification of the validated analytical method. It is suggested to adjust the method by lowering said level for Stage 2. It is possible to consider extending the range of Bioequivalence for Cmax to 70-143% in Stage 2; since the intrasubject CV was >30% and the Reference geometric mean is between 0.80-1.25 in Stage 1.

Amelioration of severe generalized idiopathic pruritus in an estrogen deficient woman taking an aromatase inhibitor for breast cancer following treatment with amphetamine salts

Purpose: To determine if treating with dextroamphetamine sulfate can relieve severe generalized idiopathic pruritus in an estrogen deficient woman taking an aromatase inhibitor for breast cancer. Materials and Methods: Dextroamphetamine sulfate 15 mg extended release capsules (as part of amphetamine salts) was prescribed. Results: Within one week the pruritus was completely dissipated and remained under total control for two months. She stopped the medication and the severe pruritus returned in three days. Resuming the amphetamine, the symptoms disappeared again and she has remained completely without symptoms for ten additional months while on medicine. Conclusions: It is not clear if the estrogen deficiency caused the pruritus by producing dry skin. Nevertheless, if a woman with estrogen deficiency complains of pruritus, but estrogen therapy is contraindicated, the treating physician could consider treating with dextroamphetamine sulfate. Of course this could be attempted in women with normal estrogen who have idiopathic pruritus in the absence of any noticeable skin lesions if other remediable causes, e.g., scabies, has been excluded.

Assessment, stratification, and monitoring of the risk for prescription opioid misuse and abuse in the primary care setting

To evaluate potential for and incidence of aberrant drug-related behaviors among patients with chronic, moderate-to-severe pain in a primary care setting and to determine investigator compliance with universal precautions (UP) approach to pain management. Open label, multicenter. Primary care centers (N = 281) across the United States. Opioid naïve and opioid experienced with chronic, moderate-to-severe pain (N = 1,487). Morphine sulfate extended-release capsules for < or = 4 months. Tools comprising UP approach were treatment agreement, card for obtaining/tracking prescriptions, Screener and Opioid Assessment for Patients with Pain-Revised questionnaire, pill counts, pain-patient follow-up tool, investigator assessment/plan, and urine drug screens (UDSs). Proportion of patients at low, moderate, and high risk of opioid misuse/abuse based on prespecified criteria and investigator judgment, proportion of patients with aberrant drug-related behaviors, and proportion of investigators compliant with UP approach. Patients were primarily white (87 percent), women (57 percent); mean age, 53 years (range, 21-92years). At baseline, 47 percent were considered low risk for opioid misuse/abuse, 52 percent moderate, and 1 percent high. UDSs were positive for illicit/nonprescribed drugs in a proportion of patients throughout the study. Overall, 64 percent of investigators were compliant with major components of UP approach in > or = 75 percent of their patients. However, there was a tendency for investigators to assign risk levels for opioid misuse/abuse as lower than protocol specified. Most patients in these primary care study centers were categorized as at least moderate risk for opioid misuse/abuse at baseline. Most primary care investigators complied with the UP approach to pain management and risk assessment. The completion of the brief training and clinical use of the tools during the study led to retained behavior change, but there was a tendency for investigators to assign lower risk levels than those that were protocol-specified, suggesting a need for better understanding of factors influencing investigator decisions.

Extended-release oral capsule of carbidopa-levodopa in Parkinson disease.

Motor fluctuations complicate the treatment of patients with Parkinson’s disease receiving levodopa. Extended-release carbidopa–levodopa has a pharmacokinetic profile that provides a more continuous levodopa serum concentration. Patients taking this formulation can expect longer duration of action and fewer doses per day, similar clinical improvement when compared to other levodopa formulations, and with a theoretically lower risk of developing motor fluctuations. Several studies, including three randomized control trials provide evidence for the efficacy, safety and tolerability of extended release carbidopa–levodopa in patients with both early and advanced Parkinson’s disease are reviewed here. Also provided is guidance for dosing of and conversion to extended release carbidopa–levodopa as well as a discussion of its place in the clinical practice.

New drugs and dosage forms

Adalimumab-adbm injection (Boehringer Ingelheim Pharmaceuticals): The biosimilar to adalimumab is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderately to severely active Crohn’s disease, moderately to severely active ulcerative colitis, or chronic moderate-to-severe plaque psoriasis. Adalimumab-adbm is also indicated for the treatment of patients 4 years of age or older with moderately to severely active polyarticular juvenile idiopathic arthritis. The tumor necrosis factor blocker is subject to FDA Medication Guide requirements. Amantadine extended-release capsules (Adamas Pharma): The drug is indicated for the treatment of dyskinesia in patients with Parkinson’s disease who are receiving levodopa-based therapy. Inotuzumab ozogamicin for injection (Besponsa, Pfizer): The antibody–drug conjugate directed against CD22 is indicated for the treatment of adults with B-cell precursor acute lymphoblastic leukemia that has relapsed or not responded to treatment. Kit for the preparation of technetium (Tc) 99m exametazime injection (Drax Exametazime, Jubilant DraxImage): Tc 99m exametazime is a radioactive diagnostic agent indicated for use during leukocyte-labeled scintigraphy imaging to localize intraabdominal infection and inflammatory bowel disease.

DEVELOPMENT AND EVALUATION OF NOVEL DRUG DELIVERY SYSTEM OF TOLTERODINE TARTRATE

Objective: Tolterodine tartrate (tolterodine) is used for treating overactive bladder (OAB) with symptoms of urinary frequency, urgency and leakage. Tolterodine is an antimuscarinic (anticholinergic) agent. It works by blocking a chemical that causes contractions of the bladder. Present work involved development of a novel drug delivery system of tolterodine intended to be taken once daily.Methods: Extended release (ER) pellets of tolterodine were prepared and optimized for in vitro drug release. Subsequently, these pellets were filled into a suitable sized capsule. The resulting capsules were evaluated for in vitro drug release. Optimized formulation was subjected to accelerated stability studies for 3 mo and was evaluated for description, average weight, assay and drug release.Results: The optimized ER capsule exhibited similar dissolution profile as that of the reference listed drug (RLD), with approximately 45%, 75% and more than 80% release in 3 h, 5 h and 7 h respectively. Accelerated stability studies indicated good physical and chemical stability of the formulation.Conclusion: ER formulation of tolterodine was optimized and can be used as once a day dosage, reducing the frequency of administration when compared with the immediate release formulation. The developed formulation exhibited similar behavior as that of reference formulation Detrol LA marketed in the US.

Cost-effectiveness of Obesity Interventions: Will We Know It When We See It?

* Abbreviations: %OBMI — : percent over BMI FBT — : family-based obesity treatment IC — : information-based control intervention ICER — : incremental cost-effectiveness ratio QALY — : quality-adjusted life year DALY — : disability-adjusted life year In this issue of Pediatrics , Quattrin et al1 present the results of a cost-effectiveness analysis of a family-based obesity treatment (FBT) program relative to an information-based control intervention (IC). The IC educated parents to encourage their children to have a weight loss goal of 0.5 to 1 lb per week. Parents then attended 16 group meetings; each meeting delivered dietary and/or physical activity advice. In between meetings, a health coach telephoned the parents to remind them to attend the meetings. The FBT group attended the same number of group meetings and received the same information. They also received education on parenting techniques both at the group sessions and during brief individual sessions with a health coach, at which time the health coach would also problem solve any concerns raised. Parents in FBT were further instructed to monitor their children’s weight and their own weight twice a week and received additional dietary (1500 and 1800 kilocalories per day for mothers and fathers, respectively), physical activity, and sedentary activity recommendations. Parents were also instructed to record food intake and activity for their children and themselves in a diary by crossing off icons detailing food groups and physical and sedentary activities undertaken. The authors report that after 2 years, child percent over BMI (%OBMI) change decreased by 1.98 U in the FBT group versus an increase of 4.37 U in the IC group. Parents lost 5.95 kg in the FBT group versus 0.16 kg in the IC group. One way to consider the impact of FBT is … Address correspondence to Eric A. Finkelstein, PhD, MHA, Health Services and Systems Research Programme, Duke-NUS Medical School, 8 College Rd, Singapore 169857. E-mail: eric.finkelstein{at}duke-nus.edu.sg