DOCSLIB.ORG

NILVAD Protocol: a European Multicentre Double-Blind Placebo-Controlled Trial of Nilvadipine in Mild-To-Moderate Alzheimer’S Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
NILVAD Protocol: a European Multicentre Double-Blind Placebo-Controlled Trial of Nilvadipine in Mild-To-Moderate Alzheimer’S Disease Open Access Protocol NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer’s disease Brian Lawlor,1 Sean Kennelly,1 Sarah O’Dwyer,1 Fiona Cregg,2 Cathal Walsh,2 Robert Coen,1 Rose Anne Kenny,1 Robert Howard,3 Caroline Murphy,3 Jessica Adams,3 Leslie Daly,4 Ricardo Segurado,4 Siobhan Gaynor,5 Fiona Crawford,6 Michael Mullan,6 Ugo Lucca,7 Rita Banzi,7 Florence Pasquier,8 Laetitia Breuilh,8 Matthias Riepe,9 Janos Kalman,10 Anders Wallin,11 Anne Borjesson,11 William Molloy,12 Magda Tsolaki,13 Marcel Olde Rikkert14 To cite: Lawlor B, Kennelly S, ABSTRACT ’ et al Strengths and limitations of this study O Dwyer S, . NILVAD Introduction: This study is a European multicentre, protocol: a European randomised, double-blind, placebo-controlled trial ▪ multicentre double-blind Large European multicentre double-blind, rando- investigating the efficacy and safety of nilvadipine as a placebo-controlled trial of mised placebo-controlled trial. nilvadipine in mild-to- disease course modifying treatment for mild-to- ▪ Investigator driven. ’ moderate Alzheimer’s moderate Alzheimer s disease (AD) in a phase III study ▪ Testing a repositioned medication with a proven disease. BMJ Open 2014;4: that will run for a period of 82 weeks with a treatment safety profile and approved for the treatment of e006364. doi:10.1136/ period of 78 weeks. hypertension. bmjopen-2014-006364 Methods and analysis: Adult patients, males and ▪ Does not test the disease modifying efficacy and females over 50 years with mild-to-moderate AD as safety of nilvadipine at the predementia stage. ▸ Prepublication history for defined by the National Institute of Neurological and this paper is available online. Communicative Disorders and Stroke/Alzheimer’s To view these files please disease and Related Disorders Association (NINCDS- visit the journal online ADRDA) criteria, will be included in the study. It aims Trial registration number: EUDRACT Reference (http://dx.doi.org/10.1136/ to recruit a total of 500 patients with AD; 250 in the Number: 2012-002764-27. bmjopen-2014-006364). nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, Received 26 August 2014 Accepted 5 September 2014 an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for INTRODUCTION a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in The current disappointing state of clinical cognitive function as assessed by the Alzheimer’s trials aimed at advancing therapeutic inter- disease Assessment Scale (ADAS-Cog 12) from ventions for Alzheimer’s disease (AD) has baseline to the end of treatment duration (78 weeks). necessitated the need for development of There are two key secondary outcome measures, the novel strategies that target multiple aspects Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) of the pathogenic process in this neurode- and the Disability Assessment for Dementia (DAD). If a generative condition. Furthermore, ideally, statistically significant effect is seen in the primary any novel drugs or compounds tested would outcome, CDR-sb will be considered to be a coprimary have a demonstrated safety profile in order end point and only the DAD will contribute to the to expedite the path to clinical application. secondary outcome analysis. Calcium antagonists or calcium channel Ethics and dissemination: The study and all fi subsequent amendments have received ethical approval blockers (CCBs) were rst introduced over For numbered affiliations see within each participating country according to national 25 years ago as coronary vasodilators for the end of article. regulations. Each participant will provide written treatment of coronary heart disease, and consent to participate in the study. All participants will have since achieved notable recognition in 1 Correspondence to remain anonymised throughout and the results of the the treatment of arterial hypertension. Prof. Brian Lawlor; study will be published in an international peer- Nilvadipine (trade name: Nivadil), a dihydro- [email protected] reviewed journal. pyridine (DHP) calcium channel antagonist, Lawlor B, et al. BMJ Open 2014;4:e006364. doi:10.1136/bmjopen-2014-006364 1 Open Access is currently licensed to treat patients with hypertension.2 required discontinuation of the medication throughout However, recent research has highlighted other proper- this study, highlighting that nilvadipine is well tolerated ties of certain CCBs, including nilvadipine, suggesting in patients with AD and has demonstrated safety as a that they are protective not just against stroke-related licensed antihypertensive treatment. dementia, but also independently against AD.3 In summary, this study will investigate the safety and Research to date has suggested that the AD preventive efficacy of nilvadipine as a disease-modifying treatment effect of DHP CCBs, may not be mediated through their in patients with mild-to-moderate AD over a period of antihypertensive effects, but rather via an anti-β-amyloid 18 months across nine countries in Europe including (Aβ) mechanism where the accumulation of Aβ in the Ireland, Germany, Greece, France, Holland, Hungary, brain is reduced by altering Aβ production in the brain Italy, Sweden and the UK. and Aβ clearance across the blood–brain barrier (BBB). Overall, the aim is to build on the initial studies of nil- Paris et al investigated the effects of a number of com- vadipine as a treatment for AD by investigating its effi- monly used antihypertensive DHPs and non-DHPs on cacy and establish its safety profile in a phase III Aβ production both in vitro and in vivo and found that double-blind, randomised, placebo-controlled trial. not all DHPs are equal. Nilvadipine and amlodipine were found to significantly lower Aβ40 as well as Aβ42 in vitro production , however, other DHPs and non-DHPs METHODS AND ANALYSIS β β had little effect or even increased A 40 and A 42 pro- Trial design in vitro in vivo duction . The studies using transgenic This is a multicentre, randomised, double-blind, placebo- mouse models of AD (Tg PS1/APPsw) highlighted nilva- controlled study of nilvadipine compared with placebo. β dipine reduced levels of A in the brain and, further- Eligible patients will be randomly assigned to receive β more, nilvadipine enhanced A clearance across the 8 mg of nilvadipine or placebo daily for 78 weeks of treat- BBB. In addition to these properties, nilvadipine has ment. Patients will initially undergo a screening assess- fi shown ef cacy against a broad range of AD pathological ment to confirm eligibility. This will be followed by a τ mechanisms, including -phosphorylation, reduced cere- baseline visit (week 0), when each patient is randomised fl fl 3 bral blood ow and neuroin ammation. and will receive the first dose of study medication. Studies have found that nilvadipine is distributed Patients will then undergo assessments at weeks 6, 13, 26, extensively throughout the body, including the brain 39, 52, 65 and 78 (±7 days) after beginning treatment. and has been shown to have a cerebrocirculatory enhan- fi 4 A nal follow-up assessment will be undertaken at cing effect. Nilvadipine has also been shown to protect 82 weeks (study end point). low-density lipoprotein cholesterol from in vivo oxidation in patients with hypertension with high risk of athero- sclerosis and to inhibit the generation of cytokines Inclusion/exclusion criteria derived from activated T lymphocytes in collagen Patients diagnosed with mild-to-moderate AD based on 56 disease complicated with essential hypertension. the National Institute of Neurological and Communicative Several epidemiological studies with different calcium Disorders and Stroke/Alzheimer’s disease and Related channel antagonists have been conducted to determine Disorders Association, Inc (NINCDS-ADRDA) criteria are their potential usefulness in the management of AD. In suitable for treatment with nilvadipine.12 See box 1 for the Systolic Hypertension in Europe (Syst-Eur) trial, details of study inclusion and exclusion criteria. which involved active treatment with the DHP CCB nitrendipine in over 2400 patients, there was a 55% reduction in the incidence of AD.7 The Baltimore Randomisation and blinding Longitudinal Study of Ageing also found a strong trend To prevent the introduction of bias, randomisation will be towards reduced relative risk of AD in patients treated via an online system, accessed via http://www.ctu.co.uk, with DHP CCBs, with no lowered risk observed in the hosted by the Clinical Trials Unit (CTU), King’s College non-DHP CCB treatment group.8 London (KCL). Eligible participants will be randomised to Furthermore, nilvadipine has been shown to have either the nilvadipine or placebo treatment group. The favourable effects on cognitive function with stabilisation nilvadipine capsules and placebo capsules will be pack- of cognitive decline and reduced conversion to AD in aged and labelled identically. Randomisation will be at the patients with hypertension with mild cognitive impair- level of the individual patient, using block randomisation ment.9 A study by Kennelly et al10 provided preliminary with randomly varying block sizes and stratified by country evidence suggesting the potential efficacy in the treat- site. Once the patient has been randomised, the online ment of AD. A 6-week open label study demonstrated system will automatically recognise which treatment packs that nilvadipine was well tolerated in patients with AD.11 are located in each study pharmacy at the recruiting study A nilvadipine slow release 8 mg formulation did not site and will randomly select a pack in the appropriate trial reduce blood pressure (BP) in non-hypertensive patients arm to be dispensed to the patient. All study staff at all with AD, but appropriately lowered BP in hypertensive sites will be blinded to treatment allocation and will cases. No patient started on nilvadipine requested or remain blind until the end of the trial.
Load more

Recommended publications
  • S Values in Accordance with Soczewiński-Wachtmeisters Equation
    S values in accordance with Soczewiński-Wachtmeisters equation S value from Antiparasitic drugs: Soczewiński’s Metronidazole Ornidazole Secnidazole Tinidazole Equation* S(m) 1.614 2.161 1.921 1.911 S(a) 1.634 2.159 1.887 1.923 S value from Antihypertensive drugs: Soczewiński’s Nilvadipine Felodipine Isradipine Lacidipine equation 4.129 4.597 3.741 5.349 S(m) S(a) 5.330 4.841 4.715 5.690 S value from Non-steroidal anti-inflammatory drugs (NSAIDs): Soczewiński’s Mefenamic Indomethacin Nabumetone Phenylbutazone Carprofen Ketoprofen Flurbiprofen equation acid 2.879 2.773 3.456 2.682 2.854 2.139 2.568 S(m) 3.317 3.442 3.910 2.404 3.394 1.968 2.010 S(a) *where: S(m) – S is the slope of the regression curie in accordance with Soczewiński-Wachtmeisters equation using methanol-water mobile phase S(a) – S is the slope of the regression curie in accordance with Soczewiński-Wachtmeisters equation using acetone-water mobile phase First group of drugs (antiparasitic drugs) 1. Metronidazole (2-Methyl-5-nitroimidazole-1-ethanol) 2. Ornidazole (1-(3-Chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole) 3. Secnidazole (1-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2ol, 1-(2Hydroxypropyl)-2-methyl-5- nitroimidazole) 4. Tinidazole (1-[2-(Ethylsulfonyl)ethyl]-2-methyl-5-nitroimidazole) Second group of drugs (antihypertensive drugs) 1. Nilvadipine (2-Cyano-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3- methyl 5-(1-methylethyl) ester, 5-Isopropyl-3-methyl-2-cyano-1,4-dihydro-6-methyl-4-(m- nitrophenyl)-3,5-pyridinedicarboxylate, FK-235, FR-34235, Isopropyl 6-cyano-5-methoxycarbonyl-2- methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate) 2.
    [Show full text]
  • Dorset Medicines Advisory Group
    DORSET CARDIOLOGY WORKING GROUP GUIDELINE FOR CALCIUM CHANNEL BLOCKERS IN HYPERTENSION SUMMARY The pan-Dorset cardiology working group continues to recommend the use of amlodipine (a third generation dihydropyridine calcium-channel blocker) as first choice calcium channel blocker on the pan-Dorset formulary for hypertension. Lercanidipine is second choice, lacidipine third choice and felodipine is fourth choice. This is due to preferable side effect profiles in terms of ankle oedema and relative costs of the preparations. Note: where angina is the primary indication or is a co-morbidity prescribers must check against the specific product characteristics (SPC) for an individual drug to confirm this is a licensed indication. N.B. Lacidipine and lercandipine are only licensed for use in hypertension. Chapter 02.06.02 CCBs section of the Formulary has undergone an evidence-based review. A comprehensive literature search was carried out on NHS Evidence, Medline, EMBASE, Cochrane Database, and UK Duets. This was for recent reviews or meta-analyses on calcium channel blockers from 2009 onwards (comparative efficacy and side effects) and randomised controlled trials (RCTs). REVIEW BACKGROUND Very little good quality evidence exists. No reviews, meta-analyses or RCTs were found covering all calcium channel blockers currently on the formulary. Another limitation was difficulty obtaining full text original papers for some of the references therefore having to use those from more obscure journals instead. Some discrepancies exist between classification of generations of dihydropyridine CCBs, depending upon the year of publication of the reference/authors’ interpretation. Dihydropyridine (DHP) CCBs tend to be more potent vasodilators than non-dihydropyridine (non-DHP) CCBs (diltiazem, verapamil), but the latter have greater inotropic effects.
    [Show full text]
  • Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options
    1521-0081/72/3/606–638$35.00 https://doi.org/10.1124/pr.120.019539 PHARMACOLOGICAL REVIEWS Pharmacol Rev 72:606–638, July 2020 Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: ERIC L. BARKER Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options Wolfgang Löscher, Heidrun Potschka, Sanjay M. Sisodiya, and Annamaria Vezzani Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany (W.L.); Center for Systems Neuroscience, Hannover, Germany (W.L.); Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University, Munich, Germany (H.P.); Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, United Kingdom (S.S); and Department of Neuroscience, Mario Negri Institute for Pharmacological Research Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy (A.V.) Abstract. ....................................................................................607 Significance Statement ......................................................................607 I. Introduction. ..............................................................................607 II. Pharmacology of Antiseizure Drugs ..........................................................608 III. In Vivo and In Vitro Models of Drug Resistance..............................................610 A. General Aspects . ........................................................................610
    [Show full text]
  • Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
    [Show full text]
  • Antioxidant Effects of Calcium Antagonists Rat Myocardial
    223 Antioxidant Effects of Calcium Antagonists ['Ii] Rat Myocardial Membrane Lipid Peroxidation Hitoshi Sugawara, Katsuyuki Tobise, and Kenjiro Kikuchi We studied the antioxidant effects of nine calcium antagonists (nisoldipine, benidipine, nilvadipine, felo- dipine, nicardipine; nitrendipine, nifedipine, verapamil, and diltiazem) by means of rat myocardial membrane lipid peroxidation with a nonenzymatic active oxygen-generating system (DHF/FeC13-ADP). The order of antioxidant potency of these agents was nilvadipine > nisoldipine > felodipine > nicardipine > verapamil > benidipine. Their IC50 values (,uM) were 25.1, 28.2, 42.0, 150.0, 266.1, and 420.0, re- spectively. In contrast, nitrendipine, nifedipine, and diltiazem had little inhibitory effect on lipid peroxi- dation.These six calcium antagonists could be divided into four types on the basis of their antioxidant mechanisms. Nilvadipine, nisoldipine, and verapamil, which showed antioxidant effects both before and after the addition of active oxygen, and reduced the dihydroxyfumarate (DHF) auto-oxidation rate, were chain-breaking and preventive antioxidants. Felodipine, which showed antioxidant effects both before and after exposure to active oxygen and increased the DHF auto-oxidation rate, was only a chain-break- ing antioxidant. Nicardipine, which showed an antioxidant effect only before exposure to active oxygen and reduced the DHF auto-oxidation rate, was mainly a preventive antioxidant. Benidipine, which showed an antioxidant effect only before exposure to active oxygen and had no appreciable effect on the DHF auto-oxidation rate, could interrupt the chain reaction of lipid peroxidation at the initial step alone. Although these results suggest that the antioxidant properties of some calcium antagonists may be beneficial clinically in protecting against cellular damage caused by lipid peroxidation, further studies are required to establish the antioxidant effects of these agents in vivo.
    [Show full text]
  • Download Leaflet View the Patient Leaflet in PDF Format
    Package leaflet: Information for the patient Carbamazepine SUN 100 mg/5 ml Oral Suspension carbamazepine Read all of this leaflet carefully before you take this medicine because it contains important information for you. − Keep this leaflet. You may need to read it again. − If you have further questions, ask your doctor or pharmacist. − This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. − If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Carbamazepine SUN is and what it is used for 2. What you need to know before you take Carbamazepine SUN 3. How to take Carbamazepine SUN 4. Possible side effects 5. How to store Carbamazepine SUN 6. Contents of the pack and other information 1. What Carbamazepine SUN is and what it is used for Carbamazepine SUN is a pale orange suspension that contains carbamazepine, the active ingredient. Carbamazepine SUN is an anti-convulsant medicine (prevents fits), it can also modify some types of pain and can control mood disorders. Carbamazepine SUN is used - to treat some forms of epilepsy - to treat a painful condition of the face called trigeminal neuralgia - to help control serious mood disorders when some other medicines don't work. 2. What you need to know before you take Carbamazepine SUN Do not take Carbamazepine SUN - if you are allergic to carbamazepine or similar drugs such as oxcarbazepine (Trileptal), or to any of a related group of drugs known as tricyclic antidepressants (such as amitriptyline or imipramine) or any of the other ingredients of this medicine (listed in section 6).
    [Show full text]
  • The Following Full Text Is a Publisher's Version
    PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/137509 Please be advised that this information was generated on 2021-09-25 and may be subject to change. BMJ Open 2014;4:e006364 doi:10.1136/bmjopen-2014-006364 Geriatric medicine Protocol NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild- to-moderate Alzheimer's disease Brian Lawlor1, Sean Kennelly1, Sarah O'Dwyer1, Fiona Cregg2, Cathal Walsh2, Robert Coen1, Rose Anne Kenny1, Robert Howard3, Caroline Murphy3, Jessica Adams3, Leslie Daly4, Ricardo Segurado4, Siobhan Gaynor5, Fiona Crawford6, Michael Mullan6, Ugo Lucca7, Rita Banzi7, Florence Pasquier8, Laetitia Breuilh8, Matthias Riepe9, Janos Kalman10, Anders Wallin11, Anne Borjesson11, William Molloy12, Magda Tsolaki13, Marcel Olde Rikkert14 + Author Affiliations 1Mercer's Institute for Research on Ageing, St. James's Hospital, Dublin, Ireland 2Trinity College Dublin (TCD), Dublin, Ireland 3King's College London (KCL), London, UK 4University College Dublin (UCD), Dublin, Ireland 5Molecular Medicine Ireland (MMI), Dublin, Ireland 6Archer Pharmaceuticals Inc, 2040 Whitefield Avenue, Sarasota, Florida, USA 7IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri” (IRFMN), Milan, Italy 8Centre Hospitalier Regional et Universitaire de Lille (CHRU- LILLE), Lille, France 9Universitaet Ulm, (UULM), Ulm, Germany 10Szegedi Tudomanyegyetem
    [Show full text]
  • PDF-Document
    Table 1. Checklist for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Reported on Section/topic # Checklist item page # TITLE Title 1 Identify the report as a systematic review, meta-analysis, or both. 1 ABSTRACT Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and Structured 2 interventions; study appraisal and synthesis methods; results; limitations; 1 summary conclusions and implications of key findings; systematic review registration number. INTRODUCTION Rationale 3 Describe the rationale for the review in the context of what is already known. 1-2 Provide an explicit statement of questions being addressed with reference to Objectives 4 participants, interventions, comparisons, outcomes, and study design 2 (PICOS). METHODS Indicate if a review protocol exists, if and where it can be accessed (e.g., Web Protocol and 5 address), and, if available, provide registration information including - registration registration number. Specify study characteristics (e.g., PICOS, length of follow-up) and report Eligibility criteria 6 characteristics (e.g., years considered, language, publication status) used as 2 criteria for eligibility, giving rationale. Describe all information sources (e.g., databases with dates of coverage, Information 7 contact with study authors to identify additional studies) in the search and 2 sources date last searched. Present full electronic search strategy for at least one database, including any Search 8 2 limits used, such that it could be repeated. State the process for selecting studies (i.e., screening, eligibility, included in Study selection 9 2-3 systematic review, and, if applicable, included in the meta-analysis). Describe method of data extraction from reports (e.g., piloted forms, Data collection 10 independently, in duplicate) and any processes for obtaining and confirming 3 process data from investigators.
    [Show full text]
  • Summary of Product Characteristics
    Health Products Regulatory Authority Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Nivadil 16mg Prolonged release capsules 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains Nilvadipine 16.0 mg For the full list of excipents, see section 6.1. 3 PHARMACEUTICAL FORM Prolonged release capsule, hard. (Prolonged release capsule) Hard gelatin capsules with an opaque brown cap (overprinted with "NV16" in white) and an opaque brown/red body containing yellow round pellets. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Nivadil is indicated for the treatment of essential hypertension. 4.2 Posology and method of administration For oral administration. The prolonged release capsule should be swallowed whole, with a little liquid, in the morning. It may be taken after breakfast. Adults The recommended dose is 1 Nivadil 8 mg prolonged release capsule per day in the morning as a starting dose. If after 2 - 4 weeks of therapy an adequate anti -hypertensive effect is not achieved, a daily dose of 16 mg nilvadipine (2 x 8 mg Nivadil prolonged release capsules, or 1 x 16 mg Nivadil prolonged release capsule, in the morning) may improve the blood pressure response. Renal impairment: No dosage adjustment is required in mild to moderate renal insufficiency. Nivadil should not however be used in patients with severe renal insufficiency. Hepatic impairment: In patients with cirrhosis of the liver, due to diminished first -pass effect, the bioavailability is increased by a factor of 2 to 3. The currently available data lead to the recommendation that a daily dose of 1 x 8 mg nilvadipine (equivalent to 1 Nivadil 8 mg prolonged release capsule) may only be exceeded under close monitoring in such patients.
    [Show full text]
  • Prescription Medications, Drugs, Herbs & Chemicals Associated With
    Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus American Tinnitus Association Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form, or by any means, without the prior written permission of the American Tinnitus Association. ©2013 American Tinnitus Association Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus American Tinnitus Association This document is to be utilized as a conversation tool with your health care provider and is by no means a “complete” listing. Anyone reading this list of ototoxic drugs is strongly advised NOT to discontinue taking any prescribed medication without first contacting the prescribing physician. Just because a drug is listed does not mean that you will automatically get tinnitus, or exacerbate exisiting tinnitus, if you take it. A few will, but many will not. Whether or not you eperience tinnitus after taking one of the listed drugs or herbals, or after being exposed to one of the listed chemicals, depends on many factors ‐ such as your own body chemistry, your sensitivity to drugs, the dose you take, or the length of time you take the drug. It is important to note that there may be drugs NOT listed here that could still cause tinnitus. Although this list is one of the most complete listings of drugs associated with tinnitus, no list of this kind can ever be totally complete – therefore use it as a guide and resource, but do not take it as the final word. The drug brand name is italicized and is followed by the generic drug name in bold.
    [Show full text]
  • Reduces Ischemic Brain Injury in Rats
    Nilvadipine, a New Calcium Channel Blocker, Reduces Ischemic Brain Injury in Rats Shoji Takakura, Teruo Susumu, Hisashi Satoh, Jo Mori, Akihiko Shiino' and Jyoji Handa' Department of Pharmacology, Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Osaka 532, Japan 'Department of Neurosurgery, Shiga University of Medical Sciences, Seta, Ohtsu 520-21, Japan Received February 7, 1991 Accepted June 10, 1991 ABSTRACT-The effects of nilvadipine, a dihydropyridine type calcium channel blocker, on cerebral infarction induced by focal brain ischemia was studied in rats. The area of infarction was measured 24 hr after occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats using triphenyltetrazolium chloride. Nilvadipine, given immediately after MCA occlusion, reduced the area of infarction significantly at doses of 0.32 mg/kg (i.p.) and 3.2, 10 and 32 mg/kg (p.o.). Nicardi pine suppressed the area of infarction at a dose of 32 mg/kg (p.o.). The results sug gest that nilvadipine is effective against ischemic brain injury. Ischemic cerebrovascular disease remains ample, it had no activity on the general be the most prevalent neurologic disorder. Cal havior in conscious dogs (T. Ono et al., un cium channel blockers have received attention published data). These results prompted us to as possible neuroprotective agents in ischemia study the effect of nilvadipine on experimental both because of their potent cerebral vasodila cerebral infarction in rats. In this study, we tory activity (1, 2) and because they may pro examined the effects of nilvadipine on the size tect neurons by preventing the accumulation of the infarction in the MCA occluded rat.
    [Show full text]
  • Drugs and Scaffold That Inhibit Cytochrome P450 27A1 (CYP27A1) in Vitro and in Vivo
    Molecular Pharmacology Fast Forward. Published on November 30, 2017 as DOI: 10.1124/mol.117.110742 This article has not been copyedited and formatted. The final version may differ from this version. MOL #110742 Downloaded from Drugs and Scaffold that Inhibit Cytochrome P450 27A1 (CYP27A1) in Vitro and in Vivo molpharm.aspetjournals.org Morrie Lam, Natalia Mast, and Irina A. Pikuleva Department of Ophthalmology and Visual Sciences, Case Western Reserve University, at ASPET Journals on September 25, 2021 Cleveland, Ohio 1 Molecular Pharmacology Fast Forward. Published on November 30, 2017 as DOI: 10.1124/mol.117.110742 This article has not been copyedited and formatted. The final version may differ from this version. MOL #110742 a) Running title: CYP27A1 Inhibition by Drugs b) Corresponding author: Irina A. Pikuleva, Department of Ophthalmology and Visual Sciences, Case Western Reserve University, 2085 Adelbert Rd., Cleveland, OH 44106. E-mail: [email protected]. Downloaded from c) 30 text pages 1 table 4 figures molpharm.aspetjournals.org 40 references 249 words in the Abstract 642 words in the Introduction at ASPET Journals on September 25, 2021 1,174 words in the Discussion d) Non-standard abbreviations: 27HC, 27-hydroxycholesterol; CTX, cerebrotendinous xanthomatosis; DHP, 1,4-dihydro-pyridine; ER, estrogen receptor; FDA, Food and Drug Administration, KPi, potassium phosphate. 2 Molecular Pharmacology Fast Forward. Published on November 30, 2017 as DOI: 10.1124/mol.117.110742 This article has not been copyedited and formatted. The final version may differ from this version. MOL #110742 ABSTRACT Cytochrome P450 27A1 (CYP27A1) is a ubiquitous enzyme that hydroxylates cholesterol and other sterols.
    [Show full text]