DOCSLIB.ORG

Spedra-Epar-Public-Assessment-Report En.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Spedra-Epar-Public-Assessment-Report En.Pdf 25 April 2013 EMA/321885/2013 Committee for Medicinal Products for Human Use (CHMP) CHMP assessment report International non-proprietary name: avanafil Procedure No. EMEA/H/C/002581/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged. Product information Name of the medicinal product: Spedra Applicant: VIVUS BV Prins Bernhardplein 200, 1097 JB Amsterdam The Netherlands Active substance: Avanafil International Nonproprietary Name/Common Avanafil Name: Pharmaco-therapeutic group Not yet assigned. (ATC Code): Therapeutic indication: Treatment of erectile dysfunction in adult men. In order for Spedra to be effective, sexual stimulation is required. Pharmaceutical form: Tablet Strengths: 50 mg, 100 mg and 200 mg Route of administration: Oral use Packaging: blister (PP/alu) Package sizes: 2 tablets, 4 tablets, 8 tablets and 12 tablets Assessment report EMA/299432/2013 Page 2/112 Executive summary Erectile dysfunction (ED) is defined as the consistent or recurrent inability to achieve and/or maintain an erection sufficient to permit satisfactory sexual performance. Normal erectile function requires the coordination of psychological, hormonal, neurological, vascular and anatomic factors. Alteration of any of these is sufficient to cause ED. The main causes of ED are chronic systemic illnesses (diabetes mellitus, heart disease, hypertension and peripheral vascular disease), neurological disorders (post-traumatic spinal-cord injuries, multiple sclerosis) or post-surgical lesions (after radical prostatectomy). There are several approaches to the management of erectile dysfunction: psychosexual counselling, hormonal therapy, mechanical devices, vascular surgery and pharmacological treatment (including intracavernosal pharmacotherapy and intra-urethral prostaglandin as well as oral treatments). The currently available oral pharmacological treatments for ED are based on inhibitors of the cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) that increase penile blood flow and erection in response to sexual stimulation. PDE type 5 (PDE5) is the predominant form of the enzyme in the smooth muscle of the corpora cavernosa. In men, sexual stimulation causes nitric oxide to be released from nerves and endothelial cells, which diffuses into smooth muscle cells in the walls of penile arteries and spongy erectile tissue. Nitric oxide stimulates the enzyme guanylate cyclase to synthesise cyclic guanosine monophosphate (cGMP), leading in turn to decreased Ca2+ concentrations in smooth muscle cells. This causes smooth muscle relaxation and increased blood flow, thus producing penile erection. In erectile tissues, cGMP is degraded by PDE5. Administration of a PDE5 inhibitor leads to higher cGMP levels and thus enhanced smooth muscle relaxation and penile blood flow. Avanafil (also referred to as TA-1790), is a new PDE5 inhibitor for oral administration that was developed for its high selectivity for the PDE5 isoenzyme relative to other PDE5 inhibitors. In April 2013, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Spedra (avanafil), for the treatment of erectile dysfunction in adult men. The recommended dose is 100 mg taken as needed approximately 30 minutes before sexual activity. Based on individual efficacy and tolerability, the dose may be increased to a maximum dose of 200 mg or decreased to 50 mg. The maximum recommended dosing frequency is once a day. In order for avanafil to be effective, sexual stimulation is required. If avanafil is taken with food, the onset of activity may be delayed compared to the fasting state. Clinical efficacy of avanafil in males with ED is supported by three phase III pivotal studies and an open-label extension study. The study design of the pivotal trials was performed in line with other available PDE5 inhibitors on the market. Unfortunately, no comparison was made with other PDE5 inhibitors to allow a better understanding of the efficacy results in the context of the current standard of care for treatment of ED. In the general population of patients with ED, avanafil, at both the 100 mg and 200 mg doses, resulted in a roughly 30% gain over placebo in the percentage of successful intercourses and 20% increase in vaginal penetration; the change in the assessment score for erectile function (delta in International Index of Erectile Function (IIEF) questionnaire) was greater than 5 points (p<0.001 for all comparisons). A comparison between the 100-mg and 200-mg doses showed no statistically significant difference. Reduced efficacy of avanafil was seen in ED subjects with diabetes mellitus. This was expected and is in line with the generally observed lower efficacy of PDE5 inhibitors in this patient population. In subjects with ED following a nerve-sparing prostatectomy, a statistically significant improvement over baseline for all three primary efficacy endpoints was observed for avanafil in subjects. Assessment report EMA/299432/2013 Page 3/112 Although the avanafil clinical development program allowed inclusion of males with no upper age limit, due to the low number of elderly subjects enrolled, it is uncertain whether efficacy and safety have been well characterised in this subgroup of subjects, especially the elderly (≥70 years old). The most common side effects are headache, flushing, nasal and sinus congestion, dyspepsia and back pain. To rule out any effect of avanafil on QTc, the Applicant has been requested to present data from a study evaluating QTc prolongation with avanafil. Furthermore the Applicant is conducting a study evaluating the effect on spermatogenesis in healthy adult male subjects, and the report will be submitted as defined in the risk management plan. So far, available data do not allow a definite conclusion on the potential risk of avanafil to the environment. The Applicant will update the interim ERA report incorporating the additional test results required and submit it to the EMA in February 2014. Overall, the efficacy of avanafil over placebo has been demonstrated. The adverse effect profile of avanafil is concordant with those known for other PDE5 inhibitors already authorised and no new safety signals have been observed with avanafil. The benefit/risk balance of avanafil in the treatment of erectile dysfunction in adult males is positive, for the intended indication “treatment of ED in adult males”. A pharmacovigilance plan for Spedra will be implemented as part of the marketing authorisation. Assessment report EMA/299432/2013 Page 4/112 Table of contents 1. Background information on the procedure .................................................................. 8 1.1. Submission of the dossier ...................................................................................... 8 1.2. Manufacturers ...................................................................................................... 9 1.3. Steps taken for the assessment of the product ......................................................... 9 2. Scientific discussion ................................................................................ 9 2.1. Introduction......................................................................................................... 9 2.2. Quality aspects .................................................................................................. 10 2.2.1. Introduction .................................................................................................... 10 2.2.2. Active Substance ............................................................................................. 11 2.2.3. Finished Medicinal Product ................................................................................ 12 2.2.4. Discussion on chemical, pharmaceutical and biological aspects .............................. 14 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 14 2.2.6. Recommendation for future quality development ................................................. 14 2.3. Non-clinical aspects ............................................................................................ 15 2.3.1. Introduction .................................................................................................... 15 2.3.2. Pharmacology ................................................................................................. 15 2.3.3. Pharmacokinetics............................................................................................. 19 2.3.4. Toxicology ...................................................................................................... 21 2.3.5. Ecotoxicity/environmental risk assessment ......................................................... 24 2.3.6. Discussion on non-clinical aspects...................................................................... 27 2.3.7. Conclusion on the non-clinical aspects ................................................................ 29 2.4. Clinical aspects .................................................................................................. 30 2.4.1. Introduction ...................................................................................................
Load more

Recommended publications
  • WO 2017/048702 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2017/048702 A l 2 3 March 2017 (23.03.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 487/04 (2006.01) A61P 35/00 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/519 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/05 1490 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 13 September 2016 (13.09.201 6) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/218,493 14 September 2015 (14.09.2015) US (84) Designated States (unless otherwise indicated, for every 62/218,486 14 September 2015 (14.09.2015) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: INFINITY PHARMACEUTICALS, INC.
    [Show full text]
  • The Single Cyclic Nucleotide-Specific Phosphodiesterase of the Intestinal Parasite Giardia Lamblia Represents a Potential Drug Target
    RESEARCH ARTICLE The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target Stefan Kunz1,2*, Vreni Balmer1, Geert Jan Sterk2, Michael P. Pollastri3, Rob Leurs2, Norbert MuÈ ller1, Andrew Hemphill1, Cornelia Spycher1¤ a1111111111 1 Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland, 2 Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems (AIMMS), Vrije a1111111111 Universiteit Amsterdam, Amsterdam, The Netherlands, 3 Department of Chemistry and Chemical Biology, a1111111111 Northeastern University, Boston, Massachusetts, United States of America a1111111111 a1111111111 ¤ Current address: Euresearch, Head Office Bern, Bern, Switzerland * [email protected] Abstract OPEN ACCESS Citation: Kunz S, Balmer V, Sterk GJ, Pollastri MP, Leurs R, MuÈller N, et al. (2017) The single cyclic Background nucleotide-specific phosphodiesterase of the Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, intestinal parasite Giardia lamblia represents a potential drug target. PLoS Negl Trop Dis 11(9): and treatment options are limited. According to the Center for Disease Control and Preven- e0005891. https://doi.org/10.1371/journal. tion, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the pntd.0005891 adult population in the developed world. This study describes the single cyclic nucleotide- Editor: Aaron R. Jex, University of Melbourne, specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new gen- AUSTRALIA eration of anti-giardial drugs. Received: December 5, 2016 Accepted: August 21, 2017 Methods Published: September 15, 2017 An extensive search of the Giardia genome database identified a single gene coding for a class I PDE, GlPDE.
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • Penile Injection Therapy | Memorial Sloan Kettering Cancer Center
    PATIENT & CAREGIVER EDUCATION Penile Injection Therapy This information will help you learn to inject medication into your penis. This is called penile injection therapy. Penile injections can help you achieve an erection if you have erectile dysfunction (ED). Read this resource carefully before starting injection therapy. If you do not follow the instructions in this resource, your doctor or APP may stop prescribing your penile injection medications and supplies. About Penile Injection Therapy The tissue that causes you to get an erection (erectile tissue) is a muscle. Going long periods of time without an erection is unhealthy for erectile tissue and may damage it. We believe having erections keeps erectile tissue healthy. A penile injection helps you have an erection. It works best if it’s given about 5 to 15 minutes before you want an erection. Penile Injection Therapy 1/19 Giving Yourself the Injection Your advanced practice provider (APP) will review the instructions below with you. Generally, the training for the injections takes 2 office visits. Please be aware that each visit may take up to 1 hour, so you should plan your schedule on the day of your appointment. Use this resource to help you the first few times you inject on your own. Do not take the following medications within 18 hours of injecting (before or after): Sildenafil (Viagra®) - 20 mg to 100 mg Vardenafil (Levitra®) - 10 mg to 20 mg Avanafil (Stendra®) - 50 mg to 200 mg If you take tadalafil (Cialis®) 10 mg or 20 mg, do not inject within 72 hours (3 days) of taking the medication.
    [Show full text]
  • Call for Methods
    CALL FOR METHODS Methods for Identification, Determination, or Screening Methods for PDE5 Inhibitors AOAC INTERNATIONAL invites method developers to submit methods for consideration and possible evaluation through the AOAC Official MethodsSM program. Prospective methods may be qualitative, identification methods, and/or screening methods for phosphodiesterase type 5 inhibitors (PDE5 inhibitors) in dietary ingredients and supplements. OBJECTIVE: The objective of this call for methods is to select and evaluate methods that can be used for routine surveillance of dietary ingredients. Acceptable methods must be reliable and reproducible when used by trained analysts in accredited laboratories. Interested method developers should provide a description of their proposed method and data characterizing the analytical performance of the proposed method. For the purpose of this Call-for-Methods, PDE5 inhibitors are defined as avanafil, lodenafil carbonate, mirodenafil, sildenafill, tadalafil, udenafil, or vardenafil; or any of their analogs. Any analytical technique that measures the analytes of interest and meets the method performance requirements specified in the SMPR will be considered. It is acceptable to have a different analytical method for each class of analytes. Applicable SMPRs: • View AOAC 2014.010 – Methods for the Identification of PDE5 Inhibitors • View AOAC SMPR 2014.011 – Methods for the Determination of PDE5 Inhibitors • View AOAC SMPR 2014.012 – Screening Methods for PDE5 Inhibitors Submit Your Method AOAC INTERNATIONAL METHOD SUBMISSION PROCESS: AOAC invites method authors to submit their methods with no fee required. Interested method authors or developers should provide a copy of their proposed method, as well as any available data characterizing the analytical performance and scientific validity of the method in AOAC format.
    [Show full text]
  • Gastroesophageal Reflux Disease (GERD)
    Guidelines for Clinical Care Quality Department Ambulatory GERD Gastroesophageal Reflux Disease (GERD) Guideline Team Team Leader Patient population: Adults Joel J Heidelbaugh, MD Objective: To implement a cost-effective and evidence-based strategy for the diagnosis and Family Medicine treatment of gastroesophageal reflux disease (GERD). Team Members Key Points: R Van Harrison, PhD Diagnosis Learning Health Sciences Mark A McQuillan, MD History. If classic symptoms of heartburn and acid regurgitation dominate a patient’s history, then General Medicine they can help establish the diagnosis of GERD with sufficiently high specificity, although sensitivity Timothy T Nostrant, MD remains low compared to 24-hour pH monitoring. The presence of atypical symptoms (Table 1), Gastroenterology although common, cannot sufficiently support the clinical diagnosis of GERD [B*]. Testing. No gold standard exists for the diagnosis of GERD [A*]. Although 24-hour pH monitoring Initial Release is accepted as the standard with a sensitivity of 85% and specificity of 95%, false positives and false March 2002 negatives still exist [II B*]. Endoscopy lacks sensitivity in determining pathologic reflux but can Most Recent Major Update identify complications (eg, strictures, erosive esophagitis, Barrett’s esophagus) [I A]. Barium May 2012 radiography has limited usefulness in the diagnosis of GERD and is not recommended [III B*]. Content Reviewed Therapeutic trial. An empiric trial of anti-secretory therapy can identify patients with GERD who March 2018 lack alarm or warning symptoms (Table 2) [I A*] and may be helpful in the evaluation of those with atypical manifestations of GERD, specifically non-cardiac chest pain [II B*]. Treatment Ambulatory Clinical Lifestyle modifications.
    [Show full text]
  • Phosphodiesterase (PDE)
    Phosphodiesterase (PDE) Phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators ofsignal transduction mediated by these second messenger molecules. www.MedChemExpress.com 1 Phosphodiesterase (PDE) Inhibitors, Activators & Modulators (+)-Medioresinol Di-O-β-D-glucopyranoside (R)-(-)-Rolipram Cat. No.: HY-N8209 ((R)-Rolipram; (-)-Rolipram) Cat. No.: HY-16900A (+)-Medioresinol Di-O-β-D-glucopyranoside is a (R)-(-)-Rolipram is the R-enantiomer of Rolipram. lignan glucoside with strong inhibitory activity Rolipram is a selective inhibitor of of 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterases PDE4 with IC50 of 3 nM, 130 nM phosphodiesterase. and 240 nM for PDE4A, PDE4B, and PDE4D, respectively. Purity: >98% Purity: 99.91% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 10 mg, 50 mg (R)-DNMDP (S)-(+)-Rolipram Cat. No.: HY-122751 ((+)-Rolipram; (S)-Rolipram) Cat. No.: HY-B0392 (R)-DNMDP is a potent and selective cancer cell (S)-(+)-Rolipram ((+)-Rolipram) is a cyclic cytotoxic agent. (R)-DNMDP, the R-form of DNMDP, AMP(cAMP)-specific phosphodiesterase (PDE) binds PDE3A directly.
    [Show full text]
  • (Medical and Mechanical) Treatment of Erectile Dysfunction
    130 SOP Conservative (Medical and Mechanical) Treatment of Erectile Dysfunctionjsm_12023 130..171 Hartmut Porst, MD,* Arthur Burnett, MD, MBA, FACS,† Gerald Brock, MD, FRCSC,‡ Hussein Ghanem, MD,§ Francois Giuliano, MD,¶ Sidney Glina, MD,** Wayne Hellstrom, MD, FACS,†† Antonio Martin-Morales, MD,‡‡ Andrea Salonia, MD,§§ Ira Sharlip, MD,¶¶ and the ISSM Standards Committee for Sexual Medicine *Private Urological/Andrological Practice, Hamburg, Germany; †The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, MD, USA; ‡Division of Urology, University of Western, ON, Canada; §Sexology & STDs, Cairo University, Cairo, Egypt; ¶Neuro-Urology-Andrology Unit, Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France; **Instituto H.Ellis, São Paulo, Brazil; ††Department of Urology, Section of Andrology and Male Infertility, Tulane University School of Medicine, New Orleans, LA, USA; ‡‡Unidad Andrología, Servicio Urología Hospital, Regional Universitario Carlos Haya, Málaga, Spain; §§Department of Urology & Urological Reseach Institute (URI), Universiti Vita Saluta San Raffaele, Milan, Italy; ¶¶University of California at San Francisco, San Francisco, CA, USA DOI: 10.1111/jsm.12023 ABSTRACT Introduction. Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interper- sonal, family, and business relationships. Aim. The aim of this study
    [Show full text]
  • The Current Treatment of Erectile Dysfunction Maria Isabela Sarbu Carol Davila University, Department of Dermatology and Venereology, Isabela [email protected]
    Journal of Mind and Medical Sciences Volume 3 | Issue 2 Article 4 2016 The current treatment of erectile dysfunction Maria Isabela Sarbu Carol Davila University, Department of Dermatology and Venereology, [email protected] Mircea Tampa Carol Davila University, Department of Dermatology and Venereology Mădălina I. Mitran Victor Babes Hospital for Infectious and Tropical Diseases, Department of Dermatology and Venereology Cristina I. Mitran Victor Babes Hospital for Infectious and Tropical Diseases, Department of Dermatology and Venereology Vasile Benea Victor Babes Hospital for Infectious and Tropical Diseases, Department of Dermatology and Venereology See next page for additional authors Follow this and additional works at: http://scholar.valpo.edu/jmms Part of the Endocrine System Diseases Commons, Marriage and Family Therapy and Counseling Commons, Psychiatry and Psychology Commons, Reproductive and Urinary Physiology Commons, and the Urology Commons Recommended Citation Sarbu, Maria Isabela; Tampa, Mircea; Mitran, Mădălina I.; Mitran, Cristina I.; Benea, Vasile; and Georgescu, Simona R. (2016) "The current treatment of erectile dysfunction," Journal of Mind and Medical Sciences: Vol. 3 : Iss. 2 , Article 4. Available at: http://scholar.valpo.edu/jmms/vol3/iss2/4 This Review Article is brought to you for free and open access by ValpoScholar. It has been accepted for inclusion in Journal of Mind and Medical Sciences by an authorized administrator of ValpoScholar. For more information, please contact a ValpoScholar staff member at [email protected]. The current treatment of erectile dysfunction Authors Maria Isabela Sarbu, Mircea Tampa, Mădălina I. Mitran, Cristina I. Mitran, Vasile Benea, and Simona R. Georgescu This review article is available in Journal of Mind and Medical Sciences: http://scholar.valpo.edu/jmms/vol3/iss2/4 J Mind Med Sci.
    [Show full text]
  • Can PDE Inhibition Improve Cognition? : Translational Insights
    Can PDE inhibition improve cognition? : Translational insights Citation for published version (APA): Reneerkens, O. A. H. (2013). Can PDE inhibition improve cognition? : Translational insights. Maastricht University. https://doi.org/10.26481/dis.20130418or Document status and date: Published: 01/01/2013 DOI: 10.26481/dis.20130418or Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.umlib.nl/taverne-license Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim.
    [Show full text]
  • Pharmaco-Induced Erections for Penile Color-Duplex Ultrasound: Oral PDE5 Inhibitors Or Intracavernosal Injection?
    International Journal of Impotence Research (2012) 24, 191 -- 195 & 2012 Macmillan Publishers Limited All rights reserved 0955-9930/12 www.nature.com/ijir ORIGINAL ARTICLE Pharmaco-induced erections for penile color-duplex ultrasound: oral PDE5 inhibitors or intracavernosal injection? Y Yang1,2, J-l Hu1,2,4,YMa1,2, H-x Wang1,2, Z Chen3, J-g Xia3, Y-x Wang1,2, Y-r Huang1,2 and B Chen1,2 To prospectively compare the clinical responses and penile color-duplex ultrasound (PCDU) results of oral PDE5 inhibitors (PDE5-Is) with papaverine intracavernosal injection (ICI) and to evaluate whether PDE5-Is could be used as alternatives to vasoactive agent injections, 25 ED patients underwent PCDU three times with an interval of at least 1 week, using different pharmacological induction: ICI mode (30--60 mg papaverine), sildenafil mode (100 mg sildenafil) and tadalafil mode (20 mg tadalafil). The preference of the patients was collected when all tests were completed. No significant differences were found in peak systolic velocity and acceleration time among all three modes. However for the ICI mode, end diastolic velocity of the right cavernosal artery was significantly higher than those of the sildenafil and tadalafil modes 5 min after erection induction, and at 15 min it became lower than those of two PDE5-I modes. Consequently, resistance index of the right cavernosal artery in ICI mode was reversed at 5 and 15 min. In all, 60.0 and 56.0% patients managed to reach full erection in PDE5-Is modes, which was significantly lower than in ICI mode (80.0%).
    [Show full text]
  • Papaverine Hydrochloride Injection, Solution American Regent, Inc
    PAPAVERINE HYDROCHLORIDE- papaverine hydrochloride injection, solution American Regent, Inc. Disclaimer: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about unapproved drugs, click here. ---------- PAPAVERINE HYDROCHLORIDE INJECTION, USP Rx Only This product is to be used by or under the direction of a physician. Each vial contains a sufficient amount to permit withdrawal and administration of the volume specified on the label. DESCRIPTION Papaverine Hydrochloride, USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine. Papaverine Hydrochloride, USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C20H21NO4•HCI. The molecular weight is 375.85. The structural formula is as shown. Papaverine Hydrochloride occurs as white crystals or white crystalline powder. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether. Papaverine Hydrochloride Injection, USP, is a clear, colorless to pale-yellow solution. Papaverine Hydrochloride, for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. The 10 mL vials also contain chlorobutanol 0.5% as a preservative. pH may be adjusted with sodium citrate and/or citric acid. CLINICAL PHARMACOLOGY The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted.
    [Show full text]