EDUCATION FROM DERMATOLOGISTS: THE SIMULTANEOUSLY DEVELOPMENT OF 16 KERATINOCYTIC CANCERS AFTER USE OF METFORMIN IN COMBINATION WITH LOSARTAN/ HYDROCHLOROTHIAZIDE, METOPROLOL AND NIFEDIPINE- IMPORTANT LINKS TO DRUG RELATED (PHOTO)-NITROSO-CARCINOGENESIS AND ONCOPHARMACOGENESIS.

Oncopharmacogenesis and Drug-Induced Skin cancer related Nitrosogenesis are newly introduced concepts in the medical literature that owe their genesis or presence to the carcinogens/ mutagens, also known as nitrosamines/NDSRIs, which are present in a heterogeneous class of drugs. The contribution to the origin of these 2 concepts is entirely due to 1) the functions and efficacy of FDA in terms of control and identification of these carcinogens, and 2) the establishment of clinicopathological correlations by the dermatologists, occurring during drug intake. According to recent FDA data, the concentration of NDMA in just one metformin tablet could be up to more than 5-fold increased. The intake of 3 to 6 tablets per day should result in a carcinogen intake that is 15 to 30 times elevated within the day and within the monomedication alone. It is these circumstances that paraphrase/ ˝betonate˝ concepts such as Onco-Pharmacogenesis and Drug-mediated Nitrosogenesis of skin cancer. Although not officially declared, these mutagens are present and have been in forced tolerance mode for the last 30-40 years. And after their intake, multiple cancers have been found to develop. The concomitant use of other nitrosamine-contaminated drugs such as losartan/hydrochlorothiazide, metoprolol and nefidipine should certainly not be surprising when it could also be associated with the development of exactly 16 keratinocytic tumours as in the case presented by us. Recent evidence in medical literature has linked the nitrosamine N-nitrosomorpholine (NMOR) with the direct development of its subsequent mutagenic action in rodents following irradiation with UVA. This fact leaves open the question of the potentially available photocarcinogenic action of the other nitrosamines in humans found in medicinal preparations. This is what necessitates a clarification of the concept of Photo-Nitroso-Carcinogenesis/ Oncogenesis in humans and its relationship to skin cancer. The overlap of the mutational patterns of some of the nitrosamine-induced mutations in target genes such as p53 and RAS oncogenes, with those of UV light-induced mutations - or practically the same ones mentioned above, suggest a possible significant role of the Drug-Induced Photo-Nitroso-Carcinogenesis of keratinocyte cancer in the context of Onco-Pharmacogenesis. Future analyses should focus on elucidating the photocarcinogenic effect of nitrosamines in drug preparations and differentiating Skin cancer Nitrosogenesis from ˝pure˝ Photo-Carcinogenesis and Nitroso-Photo-Carcinogenesis. The localization of the tumors in the area of the UV-exposed sites within the potential/actual contamination of the 4 preparations (simultaneously) in the described patient are indicative of a possible pathogenetic influence in the context of the already mentioned Nitroso-(Photo)carcinogenesis. Polycontamination of polymedication remains a so far unresolvable problem.

Comparative Bioequivalence and Food Effect of Two Formulations of 30-mg Nifedipine Controlled-Release Tablets in Healthy Chinese Adults.

Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0-∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.

Seasonal variation in ambulatory blood pressure control in patients on clinic blood pressure-guided antihypertensive treatment.

BACKGROUND: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. METHODS: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5 mg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30 mg/day, with the possible up-titration to amlodipine 10 mg/day or nifedipine-GITS 60 mg/day at 4 weeks of follow-up. RESULTS: The proportion of up-titration to higher dosages of antihypertensive drugs at 4 weeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n  = 302) than those who commenced treatment in spring/summer ( n  = 199, 24.5 vs. 12.0%, P  < 0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P  = 0.003) and 8 weeks of follow-up (52.5 vs. 74.9%, P  < 0.001). At 8 weeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8 mmHg) but greater nighttime SBP/DBP reduction (3.6/1.6 mmHg). Accordingly, at 8 weeks, the prevalence of nondippers was significantly ( P  < 0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). CONCLUSION: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.

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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Hypocalcemic tetany associated with simultaneous administration of cimetidine and nifedipine: a case report.

BACKGROUND: Acute hypocalcemia is generally caused by a sudden drop in serum calcium ion and presents with a mild or severe form of tetany. Even though the occurrence of hypocalcemia is well documented with certain drugs such as calcium chelators, bisphosphonates, and cisplatin, it is a very unusual and poorly documented adverse event with cimetidine and nifedipine. Here, we present a case of severe hypocalcemic tetany during simultaneous administration of cimetidine and nifedipine in a hypertensive patient with dyspepsia. CASE PRESENTATION: A 46-year-old known human immunodeficiency virus patient from Ethiopia on antiretroviral therapy over the past 14 years presented to the emergency department with acute exacerbation of dyspepsia and hypertensive urgency. She was given intravenous cimetidine (400 mg) and oral nifedipine (30 mg) simultaneously. One hour after the administration of these two drugs, she developed severe hypocalcemic tetany with carpopedal spasm, involuntary plantar flexion, and muscle spasms. She also had severe retrosternal chest pain and shortness of breath. Her blood pressure was 160/110 mmHg during the attack and she had no skin changes, such as urticaria. She was immediately given 1 g of calcium gluconate intravenously over 30 minutes. The carpopedal spasm progressively decreased during calcium gluconate administration. An hour later, she completely regained voluntary movement of her fingers and feet. The chest pain persisted, but resolved over the next 12 hours. The patient was discharged home after 2 days of observation. This is an unusual adverse effect that needs caution during concomitant administration of these drugs. CONCLUSIONS: Severe hypocalcemic tetany can occur with concomitant administration of cimetidine and nifedipine. Immediate treatment with calcium gluconate quickly reverses this adverse event. Concomitant administration of these drugs should be done with caution or be avoided if possible.

The Value of Injection Therapy with Botulinum Toxin in Pain Treatment of Primary Chronic Anal Fissures Compared to Anal Dilation, and Local Nifedipine in Combination with Lidocaine.

Introduction: Anal fissure is a longitudinal tear of the mucosa of the anal canal extending from the outer anal orifice in the direction of the dentate line of the inner anal opening. Fissures are divided into primary and secondary, and acute or chronic. Besides minimal rectal bleeding, itching and soiling, primary chronic anal fissures (PCAF) manifest with anal pain as theirs main determinant. It is described as the most troubling symptom. Aim: To compare the effect of injection therapy with botulinum toxin A (ITBT) vs. anal dilation (AD), and local nifedipine with lidocaine (LNL) in pain treatment of PCAF. Materials and Methods: This controlled retrospective prospective longitudinal study covered 94 patients, divided in 3 groups. The first was treated with ITBT, the second with AD and third using LNL (31, 33 and 30 patients respectively). Clostridium botulinum toxin A was used, dissolved with saline to concentration of 200 U/ml. The solution was applied to both sides of PCAF at dose of 40U. Modified technique of AD was done using 3 fingers of a single hand, progressively introduced into the anal canal, followed by gradual lateral distraction during 1 min. LNL therapy was conducted using nifedipine (0.3%) with lidocaine (1.5%) ointment, applied twice daily for 3 weeks. To measure pain, a visual analog scale (VAS) was used. The follow-up period was 12 weeks with checkup at week 4. Results: The median age of participants was 46.6±13.9 years (50 males vs. 44 females). The type of therapy had a significantly different effect on pain at week 4 (p=0.0003). Severe pain was present in only 2 ITBT patients, 16 AD, and 6 LNL patients. Post hoc analyses showed different pain disappearance time by week 12 (p <0.0001). The mean time was shortest in ITBT group (6.1±1.5 weeks). Anal pain intensity significantly differed among the 3 groups (Fisher exact, p=0.002). Namely, 71% in ITBT group rated the pain as weakest (VAS score 1) compared to 18.2% in AD and 30% of patients in LNL group. The overall pain reduction significance was in favor of ITBT, due to the differences between the ITBT and AD groups (p=0.00024) and ITBT compared to LNL group (p=0.018). Conclusion: ITBT is superior to AD and LNL in reducing pain in PCAF.

Pharmacokinetics and Bioequivalence of 2 Nifedipine Controlled-Release Tablets: A Randomized, Single-Dose, 2-Period Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

The aim of this study was to evaluate the bioequivalence of generic nifedipine controlled-release tablet compared to branded product under fasting and fed conditions. A randomized, single-dose, 2-period, crossover study with a 7-day washout period was performed in 84 healthy Chinese volunteers (fasting cohort, n = 42; fed cohort, n = 42). In each study period, volunteers were assigned to receive a single oral dose of the generic or reference product (30 mg). Blood samples were collected before dosing and up to 72 hours after administration. The plasma concentration of nifedipine was determined by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained using a noncompartmental model and log-transformed pharmacokinetic parameters (maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, AUC from time 0 to infinity) were used to evaluate bioequivalence. The results showed that the 90% confidence interval for the geometric mean ratio of pharmacokinetic parameters of the test and reference products ranged from 80.0% to 125.0% in both the fasting and fed cohorts, meeting the criteria for bioequivalence. No serious adverse events were reported throughout the study and no adverse events led to withdrawal from the study. Food effects were found in both the test and reference products, with mean maximum plasma concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity increased by 23.7%, 20.7%, and 20.5%, respectively, for the test product and 35.2%, 13.4%, and 14.7% for the reference product after a high-fat and high-calorie breakfast.

Association between clinical use of nifedipine and the risk of osteoporosis: a nationwide retrospective cohort study.

Nifedipine is one of the common calcium channel blockers (CCBs) for hypertension that induce peroxisome-proliferator-activated receptor γ coactivator 1-α, which is envisioned as a potential therapeutic target in bone disease. The findings of this retrospective cohort study suggest that patients who receive nifedipine may have a potential protective effect on osteoporosis in comparison to other CCBs. INTRODUCTION: Nifedipine was one L-type dihydropyridine calcium channel blocker (CCB) that can improve bone loss. However, epidemiological studies on the association between the use of nifedipine and osteoporosis risk are limited. Thus, this study aimed to evaluate the association between the clinical use of nifedipine and the risk of osteoporosis. METHODS: This retrospective cohort was conducted using the National Health Insurance Research Database of Taiwan from 2000 to 2013. The study includes 1225 patients receiving nifedipine (the exposed cohort) and 4900 patients receiving other CCBs (the comparison cohort). The primary outcome was the diagnosis of osteoporosis. The hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the association between the use of nifedipine and the risk of osteoporosis. RESULTS: Patients receiving nifedipine treatment had a reduced risk of osteoporosis as compared with those undergoing other CCB treatments (adjusted HR, 0.44; 95% CI, 0.37-0.53). Moreover, this inverse association is evident in both sexes and various age groups. CONCLUSIONS: This population-based cohort study demonstrated that nifedipine may have potential protective effect on osteoporosis compared with other CCBs. The clinical implications of the present study need further investigation.

Postpartum medical management of hypertension and risk of readmission for hypertensive complications.

OBJECTIVE: To compare the risk of readmission in those receiving no treatment, labetalol, nifedipine or both at hospital discharge following delivery complicated by presence of hypertension. STUDY DESIGN: Retrospective study at a single tertiary care center over a 4-year period (2017-2020). Those with peripartum hypertension (pHTN), defined as any SBP greater than 140 mmHg or DBP greater than 90 mmHg on two occasions 4 h apart during their admission for delivery were included. The primary outcome was postpartum readmission because of hypertensive complications. Analysis was stratified by medication prescribed at discharge (no treatment prescribed, labetalol, nifedipine, or both). The risks of readmission for the management of pHTN were estimated using logistic regression and adjusted for confounding variables. RESULTS: Nineteen thousand, four hundred and twenty-five women gave birth during the study period and 4660 (24.0%) met the described definition of pHTN. Of those, 1232 (26.4%) were discharged on antihypertensive medication (s). There were 217 (4.7%) readmissions for hypertensive complications following discharge. Compared with patients who did not receive antihypertensive medication at discharge, any nifedipine prescription was found to significantly decrease the risk of readmission: monotherapy [aOR 0.27 (0.15-0.48)], nifedipine with labetalol [aOR 0.35 (0.16-0.77)]. Labetalol monotherapy was associated with increased risk of readmission [aOR 1.66 (1.06-2.61)]. CONCLUSION: The risk of postpartum readmission for hypertensive complication was reduced by 65% when patients were discharged on nifedipine monotherapy and 56% with combined nifedipine and labetalol treatment when compared with no treatment. Patients discharged on labetalol monotherapy were nearly six times as likely to be readmitted for hypertensive complications when compared with patients on nifedipine monotherapy.

Efficacy and Safety of Immediate-Release Nifedipine in Critically Ill Patients.

Background: Immediate-release nifedipine (IRN) is a calcium channel blocker with potent vasodilatory and antihypertensive properties. Safety concerns led to a black box warning for increased risk of myocardial infarction, stroke, and arrhythmias. Objective: The aim of this study was to evaluate the safety and efficacy of IRN for acute blood pressure lowering in critically ill patients. Methods: A retrospective, single-center study was performed in critically ill patients who received at least one dose of IRN. The primary endpoint was the change in systolic blood pressure (SBP) measured at baseline and 1 hour after first administration of IRN. Secondary outcomes included clinically significant hypotension, defined as an absolute reduction in SBP ≥ 15% or vasopressor initiation within 1 hour after administration; incidence of arrhythmias, stroke, or myocardial injury; and time to transition off antihypertensive infusions. Results: IRN resulted in a median [interquartile range] SBP change of -10 [-21 to -1] mmHg between baseline 142 mmHg [124-155] and 1 h post-administration 127 mmHg [114-144]; P < .001. Twenty-seven percent of patients experienced clinically significant hypotension, with hypotension observed in 24% and vasopressors initiated in 4% of patients. Sixteen percent of patients experienced new-onset arrhythmia and 18% experienced myocardial injury following IRN during hospitalization. Median time to transition off intravenous (IV) continuous infusion antihypertensives was 8.5 [0-31.5] hours. Conclusion: IRN led to a reduction in SBP which may have been associated with clinically significant hypotension and need for vasopressor support. Further studies with direct comparisons to alternatives are needed to determine the true association of adverse events with IRN.

Effects of Nifedipine and Labetalol Combined with Magnesium Sulfate on Blood Pressure Control, Blood Coagulation Function, and Maternal and Infant Outcome in Patients with Pregnancy-Induced Hypertension.

Objective: The purpose is to investigate the influence of nifedipine, labetalol, and magnesium sulfate on blood pressure control, blood coagulation, and maternal and infant outcome in those suffering from pregnancy-induced hypertension (PIH). Methods: From January 2019 to April 2021, 100 participants with PIH in our center were randomly assigned to a control group and a research group. As a control, nifedipine combined with magnesium sulfate was administered. Nifedipine, labetalol, and magnesium sulfate were administered to the research group. The curative effect, blood pressure level, blood coagulation function, vascular endothelial function, and pregnancy comparisons were made between the two groups. Results: Based on the results of the study, the effective rate totaled 92.00%, while as for the control group, it was 80.0%, which indicates that there was a statistically significant difference between the effective rates of the research group and that of the control group, and the difference was statistically significant (P < 0.05). Blood pressure and blood coagulation function did not differ significantly between the two groups before treatment, and the difference was not statistically significant (P > 0.05). After treatment, both groups experienced a significant drop in systolic and diastolic blood pressure. After treatment, a higher PT index was found in the research group than in the control group. Likewise, the Fbg, D-D, and PLT were lower compared to those in the control group, and the difference was statistically significant (P < 0.05). Neither group had significantly different vascular endothelial function before treatment, and the difference was not statistically significant (P > 0.05). After treatment, the ET-1 of the two groups decreased, and the level of NO increased. There was a lower ET-1 in the research group than in the control group as well as a higher NO level in the research group than in the control group, and the difference was statistically significant (P < 0.05). Compared with the pregnancy outcome, in comparison to the controls, the research group had a higher vaginal delivery rate. Significantly, fewer cases of fetal distress, intrauterine asphyxia, and placental abruption were reported in the research group than in the control group, and the difference was statistically significant (P < 0.05). Conclusion: Nifedipine, in combination with magnesium sulfate and labetalol, is effective at treating PIH, reducing blood pressure, improving blood coagulation, preventing cardiovascular events and vascular endothelial function, and further improve the pregnancy outcome.

Bibliometric analysis of research trends and characteristics of drug-induced gingival overgrowth.

Objectives: Drug-induced gingival overgrowth (DIGO) is a frequent adverse medication reaction that is generally caused by cyclosporine, phenytoin, and nifedipine, which belong to the category of immunosuppressants, anticonvulsants, and calcium channel blockers, respectively. This bibliometric analysis aims to depict the main citation characteristics and analyze the research trends in DIGO investigations. Methods: An exhaustive search was performed in the Scopus database to create the bibliometric list of DIGO in the syntax. Furthermore, the information related to the number of citations, drugs related to DIGO, study topic and design, authorship, publication year, journal, contributing institution, country of origin, and the department was extracted. Results: In total, 399 papers on DIGO were retrieved in this study. The total number of citations and that after the removal of self-citations were 7,814 and 7,314, respectively. The mean number of citations was 19.6 in a range of 0-608. The main paper types were articles (76.94%) and reviews (19.55%). A remarkable increasing trend in the number of citations has been observed since 1994. Cyclosporine (44.89%) is the most commonly used drug that shares a close relationship with DIGO, followed by phenytoin (18.22%), nifedipine (17.93%), and amlodipine (6.81%). The review (27.82%) type constituted the most widely used design in the DIGO studies. According to the top 20 keywords, the risk factors and pathogenesis of DIGO have been prominent topics of research works for several years. Conclusions: This bibliometric analysis will facilitate the understanding of researchers and clinicians, especially those at the beginning of their careers in periodontology on DIGO, by identifying landmark research and providing an overview of this field.

Comparative efficacy and safety of oral nifedipine with other antihypertensive medications in the management of hypertensive disorders of pregnancy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hypertensive disorders of pregnancy are the most frequently occurring medical condition during pregnancy, resulting in fetal and/or maternal morbidity and mortality. This meta-analysis compared the efficacy and safety of nifedipine with other antihypertensive medications used in hypertensive disorders of pregnancy. METHODOLOGY: A comprehensive search was performed using PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. The meta-analysis was carried out using Review Manager Software, and the pooled effect estimate was generated as standardized mean difference and odds ratio with 95% confidence interval and two-sided P -value. RESULTS: The meta-analysis was comprised of 22 randomized control trials with 2595 participants. It was found that meantime and number of doses required to achieve target blood pressure were lower in the nifedipine group ( P  < 0.05). Even though it is statistically insignificant, fetal APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) scores less than seven favors nifedipine intervention. Furthermore, none of the fetal or maternal secondary outcomes were found significant. CONCLUSION: Nifedipine was found to be more effective than other antihypertensive medications to reduce blood pressure, particularly in patients with severe hypertension. However, future clinical studies, including real-world data are necessary to establish the safety profile of nifedipine concerning the fetal outcomes in hypertensive pregnant women.

Comparative efficacy of generic nifedipine versus brand-name amlodipine for hypertension management in Taiwan.

The control rate of hypertension remains concerning, indicating the requirement for better management strategies. The calcium channel blockers brand-name amlodipine and nifedipine with extended-release formulations demonstrate similar clinical efficacy. However, the efficacy of generic nifedipine remains obscure. We compared the efficacy of generic nifedipine and brand-name amlodipine in terms of cardiovascular (CV) outcomes. Patients prescribed generic nifedipine (SRFC CYH) or brand-name amlodipine besylate (Norvasc, Pfizer) between August 1, 2017, and July 31, 2018, were enrolled; patients with CV events within 3 months were excluded. CV outcomes included CV death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, hospitalization for heart failure, and composite endpoints of 3P- and 4P-major adverse cardiac events (MACE). A total of 1625 patients treated with nifedipine (SRFC CYH) and 16 587 patients treated with Norvasc were included. After propensity score matching, there were 995 and 4975 patients in the nifedipine CYH and Norvasc groups, respectively. At a mean follow-up period of 30.3 ± 6.4 months, nifedipine CYH was comparable to Norvasc in terms of CV death (P = .107), nonfatal MI (P = .121), nonfatal ischemic stroke (P = .453), hospitalization for heart failure (P = .330), 3P-MACE (P = .584), and 4P-MACE (P = .274). Cox regression analysis revealed that nifedipine CYH and Norvasc had similar efficacy in terms of 3P-MACE (hazard ratio, 0.970; 95% confidence interval, 0.601-1.565, P = .900) and 4P-MACE (hazard ratio, 0.880; 95% confidence interval, 0.628-1.233, P = .459). In conclusion, Nifedipine SRFC CYH and Norvasc have comparable clinical efficacy for hypertension management.

Nifedipine or amlodipine? The choice for hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy. OBJECTIVE: To compare antihypertensive efficacy, pregnancy outcome and safety of amlodipine with nifedipine on hypertension during pregnancy. METHODS: A systematic search of PubMed, Embase, Cochrane Library, clinicaltrials.gov, Chinese National Knowledge Infrastructure, Wanfang Database and China Biology Medicine disc of randomized controlled trials (RCTs) up to April l5, 2021 was conducted on RCTs comparing amlodipine to nifedipine for the treatment of hypertension during pregnancy. Screening, data extraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a meta-analysis was conducted. RESULTS: Seventeen RCTs were included. Amlodipine was found the efficacy is slightly superior to nifedipine on treating hypertension during pregnancy (RR 1.06, 95% CI 1.01 to 1.10) with a decreased risk for maternal side effects (RR 0.42, 95% CI 0.29 to 0.61). Subgroup analysis found amlodipine can get a better control on SBP (RR - 11.68, 95% CI - 17.98 to - 5.37) and DBP (RR - 7.44, 95% CI - 13.81 to - 1.06) compared with intermediate-/long-acting nifedipine. In addition, there was no difference between amlodipine and nifedipine on pregnancy outcomes including caesarean section, premature labour, placental abruption, FGR, fetal distress, neonatal asphyxia. CONCLUSIONS: Given the results of this systematic review and meta-analysis, amlodipine can be effectively and safely used for hypertension during pregnancy.