10-mg Tablets Research Articles

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.

Although prostate cancer is a very common form of malignancy in men, the clinical significance of androgen deprivation therapy (ADT) with abiraterone acetate versus the nonsteroidal antiandrogen bicalutamide has not yet been verified in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). The present study was designed to initiate this verification in real-world Japanese clinical practice. We retrospectively analyzed the records of 312 patients with high-risk mHSPC based on LATITUDE criteria and had received ADT with bicalutamide (n = 212) or abiraterone acetate (n = 100) between September 2015 and December 2020. Bicalutamide was given at 80 mg daily and abiraterone was given at 1000 mg daily as four 250-mg tablets plus prednisolone (5-10 mg daily). Overall survival (OS), cancer-specific survival (CSS), and time to castration-resistant prostate cancer (CRPC) were compared. The prognostic factor for time to CRPC was analyzed by Cox proportional hazard model. Patients in the bicalutamide group were older, and more of them had poor performance status (≧2), than in the abiraterone group. Impaired liver function was noted in 2% of the bicalutamide group and 16% of the abiraterone group (p < 0.001). Median follow-up was 22.5 months for bicalutamide and 17 months for abiraterone (p < 0.001). Two-year OS and CSS for bicalutamide versus abiraterone was 77.8% versus 79.5% (p = 0.793) and 81.1% versus 82.5% (p = 0.698), respectively. Median time to CRPC was significantly longer in the abiraterone group than in the bicalutamide group (NA vs. 13 months, p < 0.001). In multivariate analysis, Gleason score ≧9, high alkaline phosphatase, high lactate dehydrogenase, liver metastasis, and bicalutamide were independent prognostic risk factors for time to CRPC. Abiraterone prolonged the time to CRPC in patients with each of these prognostic factors. Despite limitations regarding the time-dependent bias, ADT with abiraterone acetate significantly prolonged the time to CRPC compared to bicalutamide in patients with high-risk mHSPC. However, further study with longer follow-up is needed.

Method development and validation of sildenafil, N-desmethylsildenafil and N1,N4-desmethylsildenafil by LC-MS/MS and its application

This study aimed to develop an LC-MS/MS method for determining sildenafil and its metabolites N-desmethylsildenafil and N1,N4-desmethylsildenafil in human plasma and applying it to a pharmacokinetic study of sildenafil in healthy volunteers. Sildenafil-d8 was used as the internal standard. Plasma samples were pretreated via protein precipitation with acetonitrile. The extractives were then separated on an ACQUITY UPLC BEH C18 (50-mm × 2.1-mm, 1.7-μm) column using gradient elution. The aqueous and organic mobile phases were ammonium formate 2 mM supplemented with 0.1% formic acid in water and acetonitrile, respectively, and the flow rate was 0.3 mL/min. An electrospray ionization source was applied, and multiple reaction monitoring was operated in the positive mode with selective channels at m/z 475.30 → 100.10, 461.20 → 283.30, 483.30 → 108.10, and 449.00 → 283.00 for sildenafil, sildenafil-d8, N-desmethylsildenafil, and N1,N4-desmethylsildenafil, respectively. The linear calibration curves of sildenafil and its metabolites spanned 1.0–1000 ng/mL. The lower limit of quantification was 1.0 ng/mL. The extractive recovery of analytes from the biological matrix was more than 90% and the matrix effect complied with relevant provisions. The intra- and inter-day precisions of sildenafil and its metabolite were <10%. The intra- and inter-day accuracy of sildenafil, N-desmethylsildenafil, and N1,N4-desmethylsildenafil was more than 99%. The method is highly sensitive and selective, and it was successfully applied to the bioequivalence studies of 100-mg sildenafil citrate tablets in 40 healthy Chinese volunteers.

Pharmacokinetic and Bioequivalence Evaluation of 2 Tadalafil Tablets in Healthy Male Chinese Subjects Under Fasting and Fed Conditions.

Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10-mg tadalafil tablets under fasted and fed conditions. This open-label, randomized, single-dose, 2-period crossover study included 53 healthy Chinese men (aged 20-43 years). Plasma samples were collected from 0.5hours before treatment to 72hours after each dose and analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration-time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high-fat, high-calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.

Caring for the Resident with Complex Medical Needs in Assisted Living

Caring for the Resident with Complex Medical Needs in Assisted Living

Safety, Patient-Reported Well-Being, and Physician-Reported Assessment of Walking Ability in Patients with Multiple Sclerosis for Prolonged-Release Fampridine Treatment in Routine Clinical Practice: Results of the LIBERATE Study.

BackgroundProlonged-release fampridine (PR-FAM) 10-mg tablet twice daily is the only approved pharmacological treatment for improvement of walking ability in adults with multiple sclerosis (MS). LIBERATE assessed the safety/effectiveness of PR-FAM in the real-world.ObjectivesThe aim of this study was to collect additional safety data, including the incidence rate of seizures and other adverse events (AEs) of interest, from patients with MS taking PR-FAM in routine clinical practice (including patients aged ≥ 65 years and those with pre-existing cardiovascular risk factors). Other objectives included change over time in patient-reported evaluation of physical and psychological impact of MS while taking PR-FAM, and change over time in physician-reported assessment of walking ability in MS patients taking PR-FAM.MethodsPatients with MS newly prescribed PR-FAM were recruited (201 sites, 13 countries). Demographic/safety data were collected at enrolment through 12 months. Physician-rated Clinical Global Impression of Improvement (CGI-I) scores for walking ability, and Multiple Sclerosis Impact Scale-29 (MSIS-29) were assessed.ResultsSafety analysis included 4646 patients with 3534.8 patient-years of exposure; median (range) age, 52.6 (21–85) years, 87.3% < 65 years, and 65.7% women. Treatment-emergent AEs (TEAEs) were reported in 2448 (52.7%) patients, and serious TEAEs were reported in 279 (6.0%) patients, of whom 37 (< 1%) experienced treatment-emergent serious AEs (TESAEs) considered related to PR-FAM. AEs of special interest (AESI) occurred in 1799 (38.7%) patients, and serious AESI in 128 (2.8%) patients. Seventeen (< 1%) patients experienced actual events of seizure. Overall, 1158 (24.9%) patients discontinued treatment due to lack of efficacy. At 12 months, a greater proportion of patients on-treatment had improvement from baseline in CGI-I for walking ability versus those who discontinued (61% vs. 11%; p < 0.001). MSIS-29 physical impact score improved significantly for patients on-treatment for 12 months versus those who discontinued (mean change, baseline to 12 months: − 9.99 vs. − 0.34 points; p < 0.001). Results were similar for MSIS-29 psychological impact.ConclusionNo new safety concerns were identified in this real-world study, suggesting that routine risk-minimization measures are effective. CGI-I and MSIS-29 scores after 12 months treatment with PR-FAM treatment show clinical benefits consistent with those previously reported.Trial RegistrationClinicalTrials.gov: NCT01480063.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00840-x.

Comparison of Clomiphene Citrate Plus N-Acetyl Cysteine and Clomiphene Citrate Alone for Induction of Ovulation in Polycystic Ovary Syndrome

Aim: To compare the frequency of ovulation with clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate alone in married females presenting with polycystic ovarian syndrome. Study design: Randomized clinical trial Place and duration of study: Department of Obstetrics and Gynaecology, Unit-3 Jinnah Hospital, Lahore from 1st September 2018 to 28th February 2019. Methodology: A total of 60 patients (30 in each group) were enrolled. In group A, females were prescribed clomiphene citrate 50-mg tablets twice daily with N-acetyl cysteine 1200 mg/day orally for 5 days starting on day 3 of the menstrual cycle and in group B, females were prescribed clomiphene citrate 50-mg tablets twice daily. Results: Patients ranged between 18-35 years of age. Mean age of the patients was 28.5±3.3 and 28.1±3.1 years in group A and B, respectively. Mean duration of marriage in group A was 3.4±0.9 and in group B 3.5±0.9 year. Mean BMI in group-A was 3.4±0.9 while in group-B 3.5±0.9 (kg/m2). Ovulation was observed at 1st month in group A was 12 (40%) and in group B 9 (30%). Ovulation was observed at 2nd month in group A was 16 (53.3%) and in group B 13 (43.3%). In 3rd months ovulation was seen in 19 patients (63.3%) of group A and 18 patients (60%) of group B. Stratification for age and BMI was also carried out. Conclusion: This study could not find any clinical superiority for clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate alone in term of ovulation rate. Keywords: N-acetyl cysteine, Polycystic ovary syndrome, Ovulation induction

In Vitro Analysis of N-Nitrosodimethylamine (NDMA) Formation From Ranitidine Under Simulated Gastrointestinal Conditions

A publication reported that N-nitrosodimethylamine (NDMA), a probable human carcinogen, was formed when ranitidine and nitrite were added to simulated gastric fluid. However, the nitrite concentrations used were greater than the range detected in acidic gastric fluid in prior clinical studies. To characterize NDMA formation following the addition of ranitidine to simulated gastric fluid using combinations of fluid volume, pH levels, and nitrite concentrations, including physiologic levels. One 150-mg ranitidine tablet was added to 50 or 250 mL of simulated gastric fluid with a range of nitrite concentrations from the upper range of physiologic (100 μmol/L) to higher concentrations (10 000 μmol/L) with a range of pH levels. NDMA amounts were assessed with a liquid chromatography-mass spectrometry method. NDMA detected in simulated gastric fluid 2 hours after adding ranitidine. At a supraphysiologic nitrite concentration (ie, 10 000 μmol/L), the mean (SD) amount of NDMA detected in 50 mL simulated gastric fluid 2 hours after adding ranitidine increased from 222 (12) ng at pH 5 to 11 822 (434) ng at pH 1.2. Subsequent experiments with 50 mL of simulated gastric fluid at pH 1.2 with no added nitrite detected a mean (SD) of 22 (2) ng of NDMA, which is the background amount present in the ranitidine tablets. Similarly, at the upper range of physiologic nitrite (ie, 100 μmol/L) or at nitrite concentrations as much as 50-fold greater (1000 or 5000 μmol/L) only background mean (SD) amounts of NDMA were observed (21 [3] ng, 24 [2] ng, or 24 [3] ng, respectively). With 250 mL of simulated gastric fluid, no NDMA was detected at the upper physiologic range (100 μmol/L) or 10-fold physiologic (1000 μmol/L) nitrite concentrations, while NDMA was detected (mean [SD] level, 7353 [183] ng) at a 50-fold physiologic nitrite concentration (5000 μmol/L). In this in vitro study of ranitidine tablets added to simulated gastric fluid with different nitrite concentrations, ranitidine conversion to NDMA was not detected until nitrite was 5000 μmol/L, which is 50-fold greater than the upper range of physiologic gastric nitrite concentrations at acidic pH. These findings suggest that ranitidine is not converted to NDMA in gastric fluid at physiologic conditions.

Preparation and Evaluation of Extemporaneously Compounded Aspirin Capsules from Crushed Aspirin Tablets

Aims: Extemporaneous preparations of medications might bring about technical and clinical consequences due to formulation failures. Therefore, all such prepared formulas should undergo valid and reliable procedures supported by solid data. Otherwise, patients can experience significant risk due to microbial contamination or physical or chemical changes during the preparation process. Thus, effective extemporaneous preparation relies on correct calculations to avoid extra and serious harm. Therefore, because 50-mg aspirin capsules are not available in Saudi Arabia, this study aimed to formulate 50-mg capsules from available 100-mg aspirin tablets.&#x0D; Methodology: Quality control tests of the preparations were carried out at the time of preparation and after one month of storage at 25 °C and at 40 °C and 75% relative humidity. All tests were carried out according to the British and United States pharmacopeia monograph of aspirin.&#x0D; Results: The drug content assay and uniformity test indicated that the aspirin capsules were within the pharmacopeial limits. The disintegration time for all aspirin capsules was within the pharmacopeial limits of 30 minutes. The aspirin release profile showed that approximately 90% of the aspirin dissolved after 10 minutes.&#x0D; Conclusion: The results indicated that the extemporaneous preparation of ASA capsules complied with the quality control tests for freshly prepared capsules and after one month of storage at room temperature and at 40 °C and 75% relative humidity. The dissolution profile of these capsules indicates immediate and high release of ASA, which is essential to ensure the required absorption. This study is of great importance for patients who need to take this dose of ASA. Pharmacists can prepare good-quality capsules with the desired ASA content using a 100-mg ASA tablet as a source of the active ingredient.

Effect of Varying Degrees of Hepatic Impairment on the Pharmacokinetics of Omecamtiv Mecarbil.

Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator under investigation for the treatment of heart failure with reduced ejection fraction. OM is primarily eliminated via metabolism mediated by multiple cytochrome P450 enzymes. This phase 1 single-dose, multicenter, open-label, nonrandomized study evaluated the pharmacokinetics (PK) of OM and major metabolites M3 and M4, safety, and tolerability following oral administration of a single dose of 25-mg MR tablet in subjects with mild (n = 6) or moderate (n = 6) hepatic impairment (according to Child-Pugh classification) versus subjects with normal hepatic function (n = 6). Relative to subjects with normal hepatic function, for subjects with mild or moderate hepatic impairment, OM AUCinf was 103.2% (90%CI, 58.0%-183.6%) and 94.8% (90%CI, 54.7%-164.1%), respectively, and OM Cmax was 126.8% (90%CI, 85.7%-187.7%) and 117.3% (90%CI, 80.7%-170.5%), respectively. Exposures to M3 were similar across groups, whereas slightly lower exposures were observed for M4 with worsening hepatic function. The OM, M3, and M4 tmax and t1/2 values were similar between groups. There were no serious adverse events (AEs) or treatment-related treatment-emergent AEs. Overall, OM, M3, and M4 PK were not meaningfully affected by mild or moderate hepatic impairment, suggesting the same dosing strategy can be used in subjects with mild or moderate hepatic impairment.

Pharmacokinetics and Bioequivalence Study of a New Branded Generic Moxifloxacin Tablet Among Healthy Volunteers.

A newly developed branded generic of a moxifloxacin (MOX) 400-mg tablet formulation was manufactured prior to this study. A bioequivalence (BE) study was done to assess the pharmacokinetics of the formulation using a randomized, open-label, 2-period crossover, 2-sequence, and single-dose experiment. Thirty healthy male volunteers were recruited. The test formulation, Flonoxin 400 mg, was compared with the reference formulation, Avelox 400 mg. The pharmacokinetic parameters of MOX were calculated based on the plasma drug concentration-time profile. Noncompartmental analysis was performed to determine its safety and tolerability. The 90% confidence intervals (CIs) were 88.5%-104.6%, 96.1%-101.1%, and 96.8%-100.7% for Cmax , AUC0-t , and AUC0-inf , respectively. All CIs were within the 80.0%-125.0% boundary, thus fulfilling the acceptable BE criteria according to the ASEAN guidelines.

Ashwagandha for reduced stress and anxiety

Ashwagandha for reduced stress and anxiety

Bioequivalence Study of Two Multivitamin Formulations Containing Vitamin E and Folate in Healthy Adults

ObjectivesBioequivalence of vitamin E and folate in a single oral dose multivitamin (MVI) gummy or tablet. MethodsThis crossover clinical trial involved healthy adults randomized to either gummy or tablet MVI containing vitamin E (VE – 279 IU gummy; 239 IU tablet) and folate (1860 μg gummy; 1877 μg tablet) as a single dose in Phase 1 with blood samples collected at pre-dose and 0.5-, 1-, 2-, 4-, 6-, 8-, 9-, 10-, 24-, and 48-hours after dosing, followed by a 2-week washout period. In Phase 2, participants crossed over to receive MVI in the form not previously given, with blood draws at the same timepoints. Maximum Concentration (Cmax), Time of Maximum Concentration (Tmax), and Area Under the Curve (AUC) were calculated for each subject for both vitamin forms. Bioequivalence for AUC, Tmax, and Cmax was defined as a 90% confidence interval (CI) for the gummy to tablet comparator ratio of the geometric mean between 80% and 125%. ResultsNineteen participants completed the study. Both gummy and tablet demonstrated absorption for both vitamins. The ratio of geometric means demonstrated bioequivalence between gummy and tablet for both VE and folate with both AUC and Cmax. While bioequivalence was also demonstrated for VE with Tmax, folate absorption peaked earlier in the gummy group (Tmax 1.89 hrs) than the tablet group (Tmax 4.00 hrs), shifting Cmax values in the gummy group to earlier timepoints than in the tablet group without affecting total absorption AUC. These results were consistent with a previous pilot study. ConclusionsOverall, under the conditions of this study, both gummy and tablet showed similar absorption of vitamin E and folate. Funding SourcesChurch & Dwight Co., Inc.

Phase 1b/2 study of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated non-small cell lung cancer who received prior therapy: Final overall survival and safety.

9048 Background: Primary findings from the phase 1b/2 study (NCT01610336) demonstrated clinical activity of combination therapy with capmatinib, a potent and selective MET inhibitor, and gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in heavily pre-treated patients with EGFR-mutated and MET dysregulated non-small cell lung cancer (NSCLC). The objective response rate (ORR) was 27% in patients across phase 1b/2 of the study. At the recommended phase 2 dose (R2PD) of capmatinib 400 mg twice-daily (bid) and gefitinib 250 mg once-daily (qd), the ORR was 47% in patients with high MET-amplified tumors ( MET gene copy number ≥6). Here, we report the updated data on the efficacy and safety from the NCT01610336 study. Methods: Patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletion or L858R mutation with a recorded clinical benefit on prior single-agent EGFR-TKI before progression and confirmed dysregulated MET pathway after progression on EGFR TKIs were included. Patients in phase 1b received capmatinib 100 to 800-mg capsules qd or 200 to 600-mg capsules or tablets bid, plus gefitinib 250 mg qd. Patients in phase 2 received the R2PD dose. Data on the overall survival (OS) and cumulative safety endpoints are reported in this final analysis. Results: Overall, 161 patients received the combination treatment in this study; phase 1b (n = 61) and phase 2 (n = 100). The median age of patients was 60.0 years, mostly Asian (67.1%) with an Eastern Cooperative Oncology Group performance status of 0/1: 18.0%/78.3%. At data cut-off on May 27, 2020, all patients had discontinued the study; 82 out of the 100 patients in phase 2 had died and 18 were censored (mostly lost to follow-up [n = 15]). One patient was still on treatment with a partial response and rolled over to another study. The median (range) follow-up time for OS was 12.2 (0.9-70.2) months. The median OS was 13.9 months (95% confidence interval, 11.6-15.7 months). The median (range) duration of exposure for capmatinib plus gefitinib was 16 weeks (0.4-209.7 weeks) during phase 1b and 18.5 weeks (0.4-268.0 weeks) during phase 2. Majority of the patients (98.8%) experienced ≥1 adverse event (AE); 87% of the patients had treatment-related AEs. Most common treatment-related AEs (reported in ≥20%) were nausea (28.0%), peripheral edema (23%), rash (21.7%), and decreased appetite (21.1%). Grade 3 or 4 treatment-related AEs occurred in 51 patients (31.7%) across both phases, of which, the most frequent (reported in ≥5%) were increased amylase and increased lipase (6.2% each) and peripheral edema (5%). Conclusions: Capmatinib 400 mg bid in combination with gefitinib 250 mg qd was well-tolerated and showed encouraging clinical activity in patients with EGFR-mutant and MET-dysregulated NSCLC. Clinical trial information: NCT01610336.

Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: study protocol for a randomized controlled trial

ObjectivesIn this study, we will investigate the effect of hydroxychloroquine on the prevention of novel coronavirus disease (COVID-19) in cancer patients being treated.Trial designThis is a two-arm, parallel-group, triple-blind, phase 2–3 randomized controlled trial.ParticipantsAll patients over the age of 15 years from 5 types of cancer will be included in the study. Patients with acute lymphoid and myeloid leukemias in the first line treated with curative intent, patients with high-grade non-Hodgkin’s lymphoma treated with leukemia regimens, and patients with non-metastatic breast and colon cancer in the first line of treatment will enter the study.Intervention and comparatorPatients are randomly assigned to two groups: one being given hydroxychloroquine and the other is given placebo. During 2 months of treatment, the two groups will be treated with hydroxychloroquine every other day with a single 200-mg tablet (Amin® Pharmaceutical Company, Isfahan, Iran) or placebo (identical in terms of shape, color, and smell). Patients will be monitored for COVID-19 symptoms during follow-up period.If any COVID-19-related signs or symptoms occur, they will be examined, thoroughly, investigated with a high resolution computerize tomography (CT) scan of the lungs and nasopharyngeal swab assessed by RT-PCR for SARS-CoV-2 virus. This study will be performed in five centers affiliated to Mashhad University of Medical Sciences, Mashhad, Iran.Main outcomesThe primary end point of this study is to investigate the incidence of COVID-19 in patients being treated for their cancer and receiving prophylactic Hydroxychloroquine.RandomizationRandomization will be performed using random permuted blocks. By using online website (www.randomization.com), the randomization sequence will be produced by quadruple blocks. The allocation ratio in intervention and control groups is 1:1.Blinding (masking)Participants and caregivers do not know whether the patient is in the intervention or the control group. Those assessing the outcomes and data analyzer are also blinded to group assignment.Sample sizeThe calculated total sample size is 60 patients, with 30 patients in each group.

Court rules no presumed malice occurred in pharmacy error case

The complexities of tapered dosing can lead to pharmacy liability if the directions given to patients are unclear or incomplete. Exposure to liability may increase when the error is not discovered at the time a prescription is refilled. This type of error was the basis of a lawsuit filed by a patient's estate against the patient's pharmacy, alleging that the patient died due to an amiodarone overdose. The patient was a 71-year-old male with chronic ischemic heart disease and atrial fibrillation. His cardiologist prescribed amiodarone 200-mg tablets. The signatura in the prescription stated: “1 TAB PO UD For Heart Rhythm 400mg 2x/day x 1 week, then 200mg 3x/day x 2 wks, then 200mg 2x/day x 2 wks, then 200mg daily” The pharmacist generated a label that read: “Take 2 tablets by mouth twice daily for 1 week – [800 mg]Then 1 tablet by mouth three times daily for two weeks – [600 mg]Then 1 tablet by mouth twice daily for 2 weeks – [400 mg]”The pharmacist omitted from the label the final part of the instructions to “then take 200 mg daily.” The pharmacist had only 60 tablets in stock, so he dispensed that number of tablets initially. He entered into the computer a quantity of 514 tablets for the prescription. Several days later, a different pharmacist dispensed the remainder of 454 tablets. The second pharmacist did not catch that the patient was to use only one tablet daily after the first 5 weeks. Six months later, a third pharmacist refilled the prescription for 514 tablets, without catching the original error. The patient died, allegedly due to “amiodarone-induced hepatotoxicity.” In the lawsuit that followed, the pharmacy did not contest liability but did move for dismissal of the plaintiff's claim for punitive damages. The court first noted that punitive damages can be awarded to a plaintiff only when there is either actual or presumed malice by the defendant. The plaintiff had not alleged actual malice by the pharmacists, so the court examined the allegation of presumed malice. Prior case law established that presumed malice requires a person to have acted “willfully or wantonly” in causing injury to another person. To prove willful or wanton misconduct, the plaintiff must prove that the defendant “knew or should have known of the substantial probability of serious physical harm and acted with a culpable mental state.” The plaintiff contended that since the pharmacists knew the adverse effects of amiodarone, the error they made was willful and wanton. The court ruled that while the pharmacists were aware of the risk of amiodarone toxicity, “awareness of the risk in and of itself does not constitute presumed malice or willful or wanton misconduct.” The court concluded that “none of the pharmacists—regardless of how irresponsibly neglectful they were or the seemingly dire consequences resulting—had the required culpable mental state by acting in some appreciable nature deliberately or intentionally.” The punitive damage allegations against the pharmacy were dismissed. Although the punitive damages claim has been dismissed, this case will continue based on the allegation of negligence and may result in an award of compensatory damages. Pharmacists can learn several important risk management lessons from the case: □When a complex tapered dose is prescribed, patient counseling can prevent misunderstandings by the patient and can correct errors by the pharmacy.□At the first refilling of prescriptions for a drug that is usually started with a loading dose, it's important to verify the maintenance dose.□Be sure to corroborate a large number of dosage units that would extend beyond a 90-day supply, particularly for a drug that is usually dosed once or twice daily.□To detect and prevent dosing errors, pay special attention to prescriptions for a drug that is labeled with a boxed warning.

Formulation, Pharmacokinetics evaluation, and IVIVC Assessment of Gliclazide Multiparticulates in Rat Model.

In vitro and in vivo studies of gliclazide (GLZ)-loaded freeze-dried alginate-gelatin (AL-GL) beads were carried out, aiming to modify its oral bioavailability. Crosslinked freeze-dried GLZ AL-GL beads (particle size: 1.5- and 3.0-mm) were prepared. In vitro evaluation of GLZ AL-GL beads included SEM, DSC, FT-IR, and release rate study in gradient media. In vivo study was single-dose (4 mg/kg), randomized, parallel-group design, two-treatment (T: test GLZ AL-GL beads and R: reference product Diamicron® 30-mg MR tablet) conducted in 96 healthy rats. Each group was subdivided into 2 sub-groups (G1 and G2) having different blood sampling schemes for up to 72 h. Assessment of level A in-vitro-in-vivo correlation (IVIVC) model was carried out. AL-GL beads successfully increased GLZ release rate compared to R. GLZ percent released (Q4h) was 109.34, 86.85, and 43.43% for 1.5-mm and 3.0-mm beads and R, respectively. DSC analysis confirmed the interaction of AL-GL via crosslinking. No chemical interaction of GLZ has occurred as proved by FT-IR. Relative bioavailability (T/R) for AUC0-∞ was 132.45% for G1 and 146.16% for G2. No significant differences between T and R in the primary pharmacokinetic parameters were determined. Tmax values were found to be earlier in the case of G1 than those of G2. A secondary absorption peak of GLZ was clearly detected in the case of R while its sharpness was minimized in T. High IVIVC was established, and hence, the proposed in vitro release model perfectly correlated with the in vivo study. The current study design might be a platform to enable panoramic view for GLZ variability in vivo.

A comparative study between the efficacy of tranexamic acid and ibuprofen for treatment of menorrhagia induced by copper T-380A intrauterine device

Background Menorrhagia is menstrual blood loss, which interferes with a woman's physical, emotional, social, and material quality of life, and which can occur alone or in combination with other symptoms. Ibuprofen is one of the most common NSAIDs used for treatment of heavy menstrual bleeding. Tranexamic acid is the best option for those who experience irregular uterine bleeding and plan to become pregnant in the near future. Objective To evaluate and compare the efficacy of tranexamic acid and ibuprofen in controlling menorrhagia induced by copper T-380A intrauterine device (IUD). Patients and methods This prospective randomized comparative parallel study between tranexamic acid and ibuprofen for treating copper-IUD-induced menorrhagia included 100 women who attend outpatient clinic at Al-Hussein University Hospital from October 2019 to March 2020. Results Mean menstrual days in both group 1 and group 2 decreased significantly from the first month after IUD insertion to 6 months after treatment. Conclusion Tranexamic acid as an antifibrinolytic agent and Ibuprofen as an NSAID, at a dosage of 500 mg capsules of tranexamic acid three times a day and 400-mg tablet of ibuprofen three times a day orally, have the same significant effects on copper T-380A IUD-induced menorrhagia. Their effects are on both the volume of blood loss and the duration of menses.

Comparative Benefits of Statins in Coronary Heart Disease

Hyperlipidemia is one of the main risk factors for coronary heart disease (CHD), thus the treatment of the lipid metabolism disorders is the main measure to prevent the development and progression of this disease. The purpose of the research is a comparative study of atorvas¬tatin, rosuvastatin, and simvastatin’s hypolipidemic effect by determining the content of a lipoprotein fraction in the dynamics of statin therapy, as well as to study their negative effect on glucose metabolism. For the study, 150 people aged (57.86 ± 4.59) years were examined for CHD (stable angina pectoris II functional class). All patients received basic CHD therapy: one 5-mg tablet of bisoprolol a day, one 75-mg tablet of aspirin a day, and short-acting nitrates for angina attacks. The patients had also been receiving statin therapy, depending on which the patients were divided into three groups (in each of 50 people): group 1 - one 20-mg tablet of simvastatin a day; group 2 - one 20-mg tablet of atorvastatin a day; group 3 - one 10-mg tablet of rosuvastatin a day. The patients taking simvastatin were observed with a significant decrease of cholesterol at the end of the 12-week treatment, by 24.7% (p < 0.05) compering to the atorvastatin group by 34.75% (p < 0.05) and rosuvastatin – by 36.96% (p < 0.05); triglycerides – by 16.2% (p < 0.05), 20.1% (p < 0.05), and 22.7% (p < 0.05), respectively; low density lipoproteins – by 24.5% (p < 0.05), 35% (p < 0.05), and 38.7% (p < 0.05) while the increase of high density lipoproteins was noted – by 20.4% (p < 0.05), 28.2% (p < 0.05), and 39.5% (p < 0.05), respectively, and AIP significantly decreased by 34% (p < 0.05), 41.8% (p < 0.05), and 64.1% (p < 0.05). Statin therapy with atorvastatin and rosuvastatin is more effective compared with simvastatin according to lipid profile, and rosuvastatin is more effective than atorvastatin based on the increase of high-density lipoproteins.

The combined effect of Algomed and a quadruple herbal brew of Iranian traditional medicine on the severity and outcome of COVID-19; a randomized controlled clinical trial recruiting inpatients

Introduction: Given the importance of coronavirus disease 2019 (COVID-19) as a worldwide issue and its health, psychological and social effects and some serious complications and consequences, it needs to find appropriate treatment for this emerging disease. Objectives: To evaluate the effectiveness of combination of Algomed and Mentha longifolia, Matricaria recutita, Althaea rosea and Malva sylvestris on the severity and outcomes of COVID-19. Patients and Methods: In a Randomized clinical trial we included 68 participants with confirmed COVID-19 through PCR tests and/or CT scan, who were admitted to non-ICU wards. The intervention group received four 300-mg Algomed tablets daily, and the quadruple herbal brew three times a day additionally while the control group received routine treatments. The brew was prepared using a large teabag containing 6 g of the four herbs (2 g of Mentha longifolia, 2 g of M. recutita, 1.4 g of Malva sylvestris and 0.6 g of A. rosea). The patients were compared daily from their admission to the end of the third day in terms of clinical and para-clinical symptoms, and outcomes. Results: The two groups were not significantly different in terms of age (P=0.657) and gender (P=0.798). The median and inter-quartile range of length of stay were respectively 3 and 2-4 days in the intervention group and 5 and 3-9 days in the controls, significantly higher in the control group (P&lt;0.001). Comparing the two groups in terms of the difference between the third and the first day values showed a significant difference in white blood cells count, a reduction of 432.9 in the intervention group vs. an increase of 65.5 in the controls (P=0.049). Except for diarrhea, which happened more in the control group (P=0.020), the two groups were not significantly different in terms of other variations. Conclusion: The present study results indicated the effects of a combination of Algomed and the brew of M. longifolia, M. recutita, A. rosea and Malva sylvestris on reducing the length of stay. It is suggested that the findings of this research should be confirmed by more detailed study with bigger sample size. It is also recommended that same or similar research should be conducted in different geographic locations of the world to confirm the outcome of this research. The main limitation of this study is that it was performed only on hospitalized patients who had a milder form of the disease in terms of disease severity. Therefore, the benefits of the interventions cannot be generalized to all patients. Trial Registration: Registration of trial protocol has been approved by Iranian Registry of Clinical Trials (#IRCT20151228025732N51, https://en.irct.ir/trial/46828, ethical code#IR.SEMUMS.REC.1398.325).

Effects of selenium intake on the expression of prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2) and matrix metallopeptidase-9 genes in the coronary artery disease: Selenegene study, a double-blind randomized controlled trial.

The oxidative stress is regarded as one of the main contributors to the health problem. Cyclooxygenase-2 (COX-2) and matrix metallopeptidase-9 (MMP-9) are two of the important genes that are reported to be involved in the cardiovascular disease (CVD) development in the molecular and genetic association studies. The aim of this study was to evaluate the level of expression of COX-2 and MMP-9 after selenium supplementation in patients with coronary artery disease (CAD). In this sub-study of Selenegene study, subjects were randomly divided into groups, 19 subjects who received selenium and 22 patients with CAD who received placebo. Patients received either 200-mg selenium yeast tablets or placebo tablets after a meal, once daily for 60 days. The messenger ribonucleic acid (mRNA) levels of the selenium and prostaglandin-endoperoxide synthase 2 (PTGS2) (COX-2) and MMP-9 genes products were determined before and after the study. In this sub-study, 41 Iranian patients with CVD were enrolled (placebo group: n = 22, selenium intervention: n = 19). Fasting blood sugar (FBS) was higher among placebo group than selenium group (93.4 ± 12.7 vs. 124.4 ± 40.6 mg/dl, P = 0.03). Triglyceride (TG) level was higher among selenium group versus placebo group (123.3 ± 34.0 vs. 184.8 ± 69.4 mg/dl, P = 0.006). The data analysis demonstrated that the expression of MMP-9 and COX-2 genes did not change significantly in both selenium and placebo groups. This study showed a positive association between the expression of MMP-9 and COX-2 in the patients with CAD who received selenium but not the placebo groups. Yet, these findings need to be confirmed in further details and expanded sample size.