Extended-release Nifedipine Research Articles

Bioavailability Study of Experimental Push–pull Osmotic Pump Tablet of Nifedipine in Dogs

This study aimed to assess the bioavailability of experimental extended-release nifedipine tablets of push-pull osmotic pump type composed of a semipermeable membrane-coated bilayer core tablet containing PEO N10 and PEO 303 in drug layer and push layer, respectively on dogs. A test on dogs was performed using a two-way randomized crossover design with a single oral dose, fasting condition. Plasma samples were obtained at intervals and analyzed for nifedipine by UPLC-MS/MS after liquid-liquid extraction using glibenclamide as the internal standard. The pharmacokinetic parameters were calculated and the bioavailability of nifedipine extended-release tablets was evaluated by comparing the pharmacokinetic parameters between the prepared extended-release tablets of 30 mg NIF and the reference tablets of Adalat LA 30 mg. It was found that the prepared push-pull osmotic pump tablets of 30 mg nifedipine were equivalent in bioavailability to Adalat LA reference tablets of 30 mg nifedipine in experimental dogs according to the regulations of US-FDA and Vietnamese pharmacopeia 5th edition. The main pharmacokinetic parameters of nifedipine test and reference tablets after a single oral administration were as follows: Cmax 26.95 ± 7.82 (ng.mL-1) and 27.20 ± 6.99 (ng.mL-1), Tmax 12.33 ± 3.44 hours and 11.50 ± 3.33 hours, AUC0-96 728.96 ± 328.87 (ng.h.mL-1) and 702.48 ± 404.48 (ng.h.mL-1), AUC0-∞, 741.05 ± 340.39 (ng.h.mL-1) and 710.71 ± 408.76 (ng.h.mL-1), MRT 21.80 ± 5.25 hours and 22.06 ± 5.20 hours, respectively. The 90% confidence intervals for the ratio of Cmax, AUC0-∞, and MRT values for the test and reference products, using logarithmically transformed data were 90.82% - 108.09%, 91.97% - 118.21%, 90.74% -107.62%, respectively. No statistically significant difference was found for the Tmax value.

Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms invivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug-drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended-release formulations, where systemic exposure of nifedipine was increased in subjects after multiple-dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well-understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically-based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in invitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two-stage invitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple-dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4-mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH-dependent formulation. The reported model-based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations.

A randomized controlled trial comparing the efficacy of nifedipine and enalapril in the postpartum period

Postpartum hypertension is a common medical complication of pregnancy and is associated with increased healthcare use, including unplanned interactions with the medical system and readmission, which can add significant stress to both a newly postpartum patient and the medical care delivery system. We currently do not know what the best antihypertensive treatment for postpartum hypertension is and tend to use antihypertensives commonly used during pregnancy. However, the mechanism of action of angiotensin-converting enzyme inhibitors may be well suited for the pathophysiology of hypertension in the postpartum period and may help to provide better control of hypertension and, in turn, decrease healthcare use. This study aimed to determine if enalapril is superior to nifedipine in preventing prolonged hospitalizations, unplanned medical visits, and/or readmission among women with postpartum hypertension. We performed an open-label, randomized controlled trial(ClinicalTrials.gov registered: NCT04236258)in which patients≥18 years with chronic hypertension, gestational hypertension, or preeclampsia were recruited to receive either 10 mg enalapril daily or 30 mg extended-release nifedipine daily as an initial antihypertensive agent in the period from delivery to 6 weeks postpartum. Recruitment occurred at a tertiary academic hospital from January 2020 to February 2021. Exclusion criteria included being on an antihypertensive when pregnancy started or requiring≥2 daily antihypertensives during pregnancy. The antihypertensive regimen was managed by the participants' obstetrical provider after the initial randomization. The primary outcome was a composite of prolonged hospitalization, unplanned clinic visits, triage visits, and/or readmission. A total of 40 patients in each arm were needed to detect a decrease in the primary outcome rate from 70% to 40% (α=0.05; power 0.80). Analyses were performed based on the intention-to-treat principal, and each arm was oversampled because of the risk for participant dropout. A total of 47 patients were randomized to each arm. Aside from the mode of delivery and twin gestation, the maternal demographics were similar between the 2 groups. The primary outcome occurred in 31 of 47 patients (66%) randomized to the nifedipine group and in 30 of 47 (64%) randomized to the enalapril group (P=.83). There was no significant difference in the primary outcome after controlling for mode of delivery and twin gestation. More patients in the enalapril arm had a second antihypertensive added during their primary hospitalization (16 vs 6) and more patients in the nifedipine arm were still on their antihypertensive at 2 weeks postpartum (42 vs 36). There were no adverse events in either group. Enalapril was not superior to nifedipine when used as an initial antihypertensive in the immediate postpartum period in terms of decreasing healthcare use.

Effect of Omeprazole Administration on the Pharmacokinetics of Oral Extended-Release Nifedipine in Healthy Subjects.

Oral extended-release (ER) dosage forms have been used to sustain blood drug levels, reduce adverse events, and improve patient compliance. We investigated potential effects of comedication on pharmacokinetic exposure of nifedipine ER products with different formulation designs and manufacturing processes. A clinical study compared a generic version of nifedipine ER tablet with pH-dependent dissolution behavior with an osmotic pump product with pH independent drug release under fasting condition. In this study, two nifedipine tablet products were tested with or without short-term omeprazole comedication in healthy subjects. Seven-day administration of omeprazole before nifedipine dosing significantly increased the gastric pH, and subsequently increased the geometric least square (LS) means of area under the concentration-time curve from time zero to the last measurable timepoint (AUC0-t ) and maximum plasma concentration (Cmax ) of nifedipine to 132.6% (90% confidence interval (CI): 120.6-145.7%) and 112.8% (90% CI: 100.8-126.3%) for pH-dependent ER tablets, and 120.6% (90% CI: 109.7-132.5%) and 122.5% (90% CI: 113.7-131.9%) for the pH-independent ER tablets, respectively. Similar extent of increase in AUC0-t and Cmax was confirmed in the subpopulations whose gastric pH was ≥ 4 or ≤ 3 in subjects with or without omeprazole administration. Given that similar increases in drug exposures were observed for both pH-dependent and pH-independent nifedipine formulations and the geometric LS mean ratios were between 112% and 133% with and without short-term omeprazole comedication, the gastric pH may have limited effects on omeprazole-induced nifedipine PK changes on the tested formulations. The inhibition of cytochrome P450 3A4 activity may play a significant role causing nifedipine exposure changes for both formulations, which would warrant additional assessment.

Blood pressure medication use and postpartum hospital readmission among preeclampsia patients

ABSTRACT Background Blood pressure medication is often prescribed to patients with preeclampsia. We are not aware of any study on readmission of those with preeclampsia to the hospital that considers blood pressure medication use or dose. Methods This was a retrospective study of 440 preeclampsia patients diagnosed during the antepartum, intrapartum, or immediate postpartum period prior to discharge from the hospital. The outcome was hospital readmission. One analysis compared blood pressure medication (oral labetalol and oral extended release nifedipine) use and nonuse. Another analysis compared low-dose and high-dose blood pressure medication use. Results Blood pressure medication use was not significantly associated with readmission (OR: 0.79, 95% CI: 0.39, 1.63, p = 0.53). Low dose of blood pressure medication was significantly associated with increased odds for readmission (OR: 2.29, 95% CI: 1.00, 5.25, p = 0.05). Conclusion We found that low dose of blood pressure medication was associated with increased odds for readmission within 6 weeks among those with preeclampsia. We recommend that clinicians balance the preference to reduce a blood pressure medication dose with the possible concern that too low a dose may place certain patients on track for hospital readmission after discharge.

Postpartum Discharge on Labetalol was Associated with Increase Risk of Readmission for Hypertension Compared with Discharge on Nifedipine

Introduction: Hypertension complicating pregnancy is common and, when uncontrolled, can have devastating consequences. Objectives: The main objective of the study is to find the postpartum discharge on labetalol was associated with increase risk of readmission for hypertension compared with discharge on nifedipine. Material and methods: This cross-sectional study was conducted in Islam medical college and teaching hospital Sialkot during June 2022 to September 2022. The data was collected with the permission of ethical committee of hospital. Data was collected with the permission of ethical committee of hospital. Participants were randomized to labetalol versus extended release nifedipine using a computerized random number generator. Results: Data was collected from 50 female patients. Baseline maternal characteristics were similar between groups, including age, race, body mass index (BMI), gravidity and parity, rate of twins, and presence of medical comorbidities including chronic hypertension. Data was collected in two groups, one group of labetalol and second group of nifedipine. Practical implication: This study will help us to find the efficacy of both the drugs that we used in the study for the purpose of postpartum hypertension. Conclusion: It is concluded that both oral labetalol and oral extended release nifedipine are effective and well tolerated for management of postpartum hypertension. Keywords: Hypertension, Postpartum, Oral, Management, Labetalol, Nifedipine

Comparison of pregnancy latency in preterm preeclampsia with oral labetalol versus extended-release nifedipine

Comparison of pregnancy latency in preterm preeclampsia with oral labetalol versus extended-release nifedipine

Preparation of Nifedipine Push-Pull Osmotic Pump Tablets

This study aims to investigate the influence of the formulation factors on the drug release kinetics, thereby selecting the compositions of extended-release nifedipine tablet based on the similarity coefficient f2 obtained when compared with Adalat LA tablet. The formulation factors such as: molecular weight of the polyethylene oxide (PEO) and osmotic agent amount in drug layer and push layer, semi permeable membrane thickness (estimated by coating weight gain), orifice size, type of plasticizers and ratios of coating polymer to plasticizer in semipermeable membrane were evaluated. It was found that developed tablets were able to deliver nifedipine in an approximate zero-order manner up to 20 hours and drug release profile of developed tablets was similar to that from Adalat LA tablets. The developed tablet contained: PEO N10, PEO 303 in drug layer and push layer, respectively; percentages of osmotic agent in drug layer and push layer were 10% and 30%, respectively; weight gain of semipermeable coating was 12%; and orifice size was 0.8 mm.
 Keywords
 Nifedipine, GPKD, push-pull osmotic pump, PEO, Tlag.
 References
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Investigation of Some Modifiable Risk Factors That Lead to Congenital Anomalies: A Review Article

Background: Congenital anomalies are inborn errors of development. Genetic and environmental factors are known causes of congenital anomalies. Environmental factors are modifiable risk factors. This review focuses on modifiable risk factors for birth defects. There is a strong link between alcohol use and an increased risk of congenital anomalies. Marijuana can be expected to cause fetal growth restriction; smoking before conception, even with cessation in the first trimester, may also pose a risk for gastroschisis. Benzodiazepines during the first trimester were associated with Dandy–Walker malformation ,anophthalmia or microphthalmia and esophageal atresia. While oral retinoids are absolutely contraindicated, topical retinoids, should conservatively be avoided during pregnancy but if were used by accident, the existing data can reduce the anxiety of happening adverse pregnancy outcomes. Antihypertensives such as labetalol, methyldopa and extended release nifedipine are relatively safe choices. Antiemeticssuch as doxylamine-pyridoxine and metoclopramide may have potential teratogenicity in first trimester. Ondansetron use was not significantly associated with major congenital anomalies but recent meta-analysis suggested more concern. An antiepileptic such as valproate poses the highest risk among antiepileptic drugs, whereas the prevalence of congenital anomalies is the lowest with lamotrigine, levetiracetam, and oxcarbazepine. Education and counseling to women who are planning to become pregnant can reduce the risk of congenital anolamies.

Comparison of short-acting versus extended-release nifedipine: Effects on hemodynamics and sympathetic activity in patients with stable coronary artery disease

We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7–10 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6 hours. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30 minutes) and was much greater than that observed in the extended release group, which occurred later (270 minutes). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation.

Clinical Reasoning: A 43-year-old woman with right limb weakness

A 43-year-old woman presented with a 4-day history of right limb weakness. While biking 4 days earlier, she felt a weakness in her right hand and leg. She had a history of hypertension for more than 2 years, and was taking extended-release nifedipine tablets (40 mg) and perindopril (4 mg) daily, but her blood pressure was difficult to control (fluctuations of 150–180/90–115 mm Hg). The patient did not smoke or drink alcohol, and had no family history of similar diseases. The authors thank Dr. Haiyan Lou and Dr. Xiaodong Teng for their contributions.

Oral labetalol compared to oral nifedipine for postpartum hypertension: A randomized controlled trial

ABSTRACTObjective: To determine whether oral labetalol is associated with a shorter time to blood pressure control compared to oral extended release nifedipine for management of persistent postpartum hypertension. Study Design: This randomized controlled trial conducted between June 2014 and June 2015 included women who delivered at ≥32 weeks’ gestation with persistent postpartum hypertension (sustained blood pressure ≥150/100 mmHg) requiring an oral antihypertensive agent. We included women with gestational hypertension, preeclampsia, or chronic hypertension not previously on medication. Women were randomized to labetalol or nifedipine, and the allocated study drug was incrementally increased to achieve blood pressure control. The primary outcome was time to sustained blood pressure control defined as the absence of severe hypertension for at least 12 hours. Secondary outcomes included postpartum length of stay, need for increased dosing, need for additional oral antihypertensive agents, and patient reported side effects. Twenty women were needed in each group as determined by the sample size calculation. Results: We randomized 25 women to oral labetalol and 25 women to oral extended release nifedipine. The time to achieve BP control was similar between labetalol and nifedipine groups (37.6 hours versus 38.2 hours, p = 0.51). Secondary outcomes including postpartum length of stay, need for increased dosing, and need for additional oral antihypertensive agents were similar between groups. For women discharged on a single agent, significantly more subjects in the labetalol group (16/21) compared to the nifedipine group (10/22) achieved BP control with the initial starting dose (76% versus 46%, p = 0.04). No major side effects were observed. Minor side effects were significantly more common in women taking nifedipine compared to labetalol (48% versus 20%, p = 0.04). Conclusions: Both labetalol and nifedipine were effective for control of persistent postpartum hypertension. However, labetalol achieved control significantly more often with the starting dose and had fewer side effects. Clinical Trial Registration: Oral nifedipine versus oral labetalol, NCT02168309. https://clinicaltrials.gov/ct2/show/NCT02168309?term=labetalol+versus+nifedipine&rank=2

40: Oral labetalol compared to oral extended release nifedipine for persistent postpartum hypertension: a randomized controlled trial

40: Oral labetalol compared to oral extended release nifedipine for persistent postpartum hypertension: a randomized controlled trial

Comparison of antihypertensive effects and treatment compliance of extended release nifedipine tablets and nifedipine controlled release tablets

Objective To study the antihypertensive effects and treatment compliance of extended release nifedipine tablets and nifedipine controlled release tablets. Methods 120 cases of patients with hypertension from April 2012 to April 2013, with informed consent of patients and in accordance with the medical ethics standard, were divided into the group I and group II of 60 cases in each group according to the random number table method, the group I was given extended release nifedipine tablets for treatment while the group II was given nifedipine controlled release tablets for therapy, antihypertensive effect, treatment compliance and adverse reaction of two groups were compared. Results The total efficiency of group II was 93.3%,which was higher than 80.0% of the group I,there was statistically significant differences between the two groups(χ2= 12.019,P = 0.019); The adverse reaction rate of group II was 8.3%,which was significantly lower than 18.3% of the group I,there was statistically significant differences between the two groups(χ2= 11.271,P= 0.021);The treatment compliance of group II was 96.7%,which of the group I was 95.0%,there was no significant differences between the two groups(χ2= 5.419,P= 0.067). Conclusion Nifedipine controlled release tablets has a better antihypertensive effect, with less adverse reaction when compared with nifedipine controlled release tablets. Key words: Extended Release Nifedipine Tablets; Nifedipine Controlled Release Tablets; Antihypertensive effect; Compliance

Extended-release nifedipine and the risk of intestinal obstruction: a population-based study

ObjectivesTo examine the risk of bowel obstruction in older adults during treatment with extended-release nifedipine compared with patients treated with amlodipine.DesignRetrospective cohort study using multiple linked healthcare databases.SettingOntario, Canada from...

Extreme bradycardia due to multiple drug–drug interactions in a patient with HIV post‐exposure prophylaxis containing lopinavir–ritonavir

Extreme bradycardia due to multiple drug–drug interactions in a patient with HIV post‐exposure prophylaxis containing lopinavir–ritonavir

Potential Protective Effect of Long-Term Therapy with Xuezhikang on Left Ventricular Diastolic Function in Patients with Essential Hypertension

To investigate the benefits of long-term therapy with Xuezhikang, a cholestin extract, in combination with calcium channel blockers for improvement of left ventricular (LV) hypertrophy and function in patients with essential hypertension, as determined using echocardiography. Fifty-five (55) hypertensive patients with normal blood low-density lipoprotein cholesterol (LDL-C) levels were randomly assigned to the Xuezhikang group (n = 28, 1200 mg/d of Xuezhikang) or the placebo group (n = 27, matched placebo). All of the patients were treated with extended-release nifedipine (20 mg twice daily). Thirty (30) normotensive subjects, matched for age and gender, were selected as a control group. Conventional echocardiography and tissue Doppler imaging were used to measure the left ventricle (LV) wall thickness and LV diastolic function at weeks 0, 24, and 72 during the period of observation. The serum levels of lipids, carboxy-terminal propeptide of procollagen type I (PIP), and C-reactive protein (CRP) were determined as well. The hypertensive patients had significantly elevated PIP and CRP levels in serum, increased LV wall thickness, and impaired LV diastolic function compared with the normotensive subjects (0.01 < p < 0.05). Compared with the placebo group, the transmitral flow velocities (E/A ratio) (1.11 +/- 0.36 versus 0.85 +/- 0.24, p < 0.01) and the myocardial motion velocities (Em/Am ratio) at the septal mitral annulus (0.90 +/- 0.19 versus 0.70 +/- 0.18, p < 0.05) and the lateral mitral annulus (1.06 +/- 0.20 versus 0.86 +/- 0.14, p < 0.01) were significantly increased, while there was no significant change in the LV wall thickness after 72 weeks of therapy with Xuezhikang. The serum levels of PIP (0.43 +/- 0.13 ng/mL versus 0.51 +/- 0.20 ng/mL, p < 0.05) and CRP (0.32 +/- 0.13 mg/L versus 0.40 +/-0.17 mg/L, p < 0.05) were significantly reduced compared to placebo treatment. There was no significant correlation between changes in LV diastolic function and blood pressure or lipid profile with Xuezhikang therapy. Long-term therapy with Xuezhikang improved LV diastolic function, probably mediated through antifibrotic and anti-inflammatory effects and independent of blood pressure and lipid profiles in patients with essential hypertension.

Investigation of the Dissolution Characteristics of Nifedipine Extended-Release Formulations Using USP Apparatus 2 and a Novel Dissolution Apparatus

The aim of our studies was to investigate the dissolution characteristics of six extended-release nifedipine tablets with a dosage strength of 20 mg that are marketed in the European Union. All investigated products were homogenous matrix tablets having identical dosing regimens. The products can be substituted for originator products and other ER generic formulations of the same drug load. In the present study, the formulations were tested using USP Apparatus 2 at 50 rpm, which is one of the standard conditions specified by the USP for nifedipine ER tablets. Moreover, investigations under intensified stress conditions were performed with Apparatus 2 at 100 rpm, as well as in a novel biorelevant dissolution stress-test device. A complementary characterization of the integrity of the tablet matrices was performed using a standard disintegration test apparatus. In the applied experimental settings, drug dissolution from all tested formulations proceeded very fast with liberation of at least 15 mg of drug within the first two hours of analysis. The increase in stirring rate from 50 to 100 rpm in Apparatus 2 did not substantially accelerate the dissolution process. Moreover, it was noticed that the tablet matrices had poor mechanical stability and very rapid disintegration behavior under all experimental settings. The disintegration times measured in the standard disintegration test were less than 10 min. The results clearly show that the dissolution characteristics of all tested products are a function of the properties of the drug substance and not the dosage forms. It became obvious that none of the tested formulations fulfilled USP requirements for nifedipine ER tablets specified for Apparatus 2 at 50 rpm. However, the products are marketed in the European Union where the USP quality criteria are not mandatory but only advisable. In our interpretation, such dissolution characteristics bear a potential risk of dosage-form-related interactions in vivo.

Dihydropyridine calcium channel blockers and cardiovascular outcomes in elderly patients: A population-based study

Dihydropyridine calcium channel blockers are widely used for the treatment of hypertension and angina. Despite safety concerns associated with short-acting agents, increasing evidence supports the safety of long-acting dihydropyridines. Although amlodipine is the best studied of these, there are few studies comparing it with nifedipine. To examine the association between hospitalization for acute coronary syndromes and treatment with amlodipine or extended-release nifedipine in patients 65 years of age and older. The primary objective was a composite of hospital admission for angina or acute myocardial infarction. The present population-based, retrospective cohort study used linked health care databases from Ontario. Propensity scores were used to identify highly similar patients started on amlodipine or extended-release nifedipine between April 1997 and March 2002. Time-to-event analysis was conducted using Cox proportional hazards models. The analysis included 24,190 patients (44% male; mean age 75 years) treated with amlodipine or extended-release nifedipine (n=12,095 each). The number of patients reaching the primary end point was 362 (3%) and 294 (2.4%) in the amlodipine and nifedipine groups, respectively. The groups were similar in a large number of demographic and clinical characteristics. No significant differences were observed among users of extended-release nifedipine (adjusted hazard ratio 0.91, 95% CI 0.74 to 1.13) relative to amlodipine. These findings suggest that amlodipine and extended-release nifedipine are not associated with differential rates of acute coronary events in older patients.

Bezoar Formation Requiring Endoscopic Removal After Intentional Overdose of Extended-Release Nifedipine

A 61-year-old Caucasian woman was transported to the emergency department after intentionally ingesting several different prescription drugs. She had been found by her husband in an unconscious state with empty bottles of extended-release venlafaxine, extended-release nifedipine, sertraline, and atorvastatin. She was intubated in the emergency department and transferred to the intensive care unit. After 36 hours in the intensive care unit, she was stabilized and brought to a general medical ward. She later developed profound recurrent hypotension with systolic blood pressures ranging from 40-70 mm Hg and diastolic blood pressures of 0-40 mm Hg. She was readmitted to the intensive care unit, where a computed tomography scan revealed a mass in her stomach. A gastroenterology consultation was obtained, and an esophagogastroduodenoscopy (EGD) was performed, during which a large drug bezoar was discovered and removed. The drugs were identified as extended-release nifedipine with a few granules of extended-release venlafaxine. Unfortunately, the patient died 3 days after the EGD from multisystem organ failure related to the overdose. Clinicians who encounter drug overdoses should be aware of the possibility of drug bezoar formation and should consider endoscopic removal as a potential treatment option.