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DDAVP Nasal Spray Is Provided As an Aqueous Solution for Intranasal Use
DDAVP® Nasal Spray (desmopressin acetate) Rx only DESCRIPTION DDAVP® Nasal Spray (desmopressin acetate) is a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation. It is chemically defined as follows: Mol. wt. 1183.34 Empirical formula: C46H64N14O12S2•C2H4O2•3H2O 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate. DDAVP Nasal Spray is provided as an aqueous solution for intranasal use. Each mL contains: Desmopressin acetate 0.1 mg Sodium Chloride 7.5 mg Citric acid monohydrate 1.7 mg Disodium phosphate dihydrate 3.0 mg Benzalkonium chloride solution (50%) 0.2 mg The DDAVP Nasal Spray compression pump delivers 0.1 mL (10 mcg) of DDAVP (desmopressin acetate) per spray. CLINICAL PHARMACOLOGY DDAVP contains as active substance desmopressin acetate, a synthetic analogue of the natural hormone arginine vasopressin. One mL (0.1 mg) of intranasal DDAVP has an antidiuretic activity of about 400 IU; 10 mcg of desmopressin acetate is equivalent to 40 IU. 1. The biphasic half-lives for intranasal DDAVP were 7.8 and 75.5 minutes for the fast and slow phases, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone used in this condition. As a result, intranasal DDAVP provides a prompt onset of antidiuretic action with a long duration after each administration. 1 2. The change in structure of arginine vasopressin to DDAVP has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle. -
Vasopressin in Pediatric Critical Care
182 Review Article Vasopressin in Pediatric Critical Care Karen Choong1 1 Department of Pediatrics, Critical Care, Epidemiology and Address for correspondence Karen Choong, MB, BCh, MSc, Biostatistics, McMaster University, Hamilton, Ontario, Canada Department of Pediatrics, Critical Care, Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Room 3E20, J Pediatr Intensive Care 2016;5:182–188. Hamilton, Ontario, Canada L8S4K1 (e-mail: [email protected]). Abstract Vasopressin is a unique hormone with complex receptor physiology and numerous physiologic functions beyond its well-known vascular actions and osmoregulation. While vasopressin has in the past been primarily used in the management of diabetes insipidus and acute gastrointestinal bleeding, an increased understanding of the physiology of refractory shock, and the role of vasopressin in maintaining cardiovascular homeostasis prompted a renewed interest in the therapeutic roles for this hormone in the critical care setting. Identifying vasopressin-deficient individuals for the purposes of assessing responsiveness to exogenous hormone and prognosticating outcome has expanded research into the evaluation of vasopressin and its precursor, copeptin as Keywords useful biomarkers. This review summarizes the current evidence for vasopressin in ► vasopressin critically ill children, with a specific focus on its use in the management of shock. We ► pediatrics outline important considerations and current guidelines, when considering the use of ► shock vasopressin or its -
Glypressin Ferring Pharmaceuticals Pty Ltd PM-2010-03182-3-3 Final 26 November 2012
Attachment 1: Product information for AusPAR Glypressin Ferring Pharmaceuticals Pty Ltd PM-2010-03182-3-3 Final 26 November 2012. This Product Information was approved at the time this AusPAR was published. Product Information ® GLYPRESSIN Solution for Injection NAME OF THE MEDICINE Terlipressin (as terlipressin acetate). The chemical name is N-[N-(N-Glycylglycyl)glycyl]-8-L- lysinevasopressin. Terlipressin has an empirical formula of C52H74N16O15S2 and a molecular weight of 1227.4. CAS No: 14636-12-5. The pKa is approximately 10. Terlipressin is freely soluble in water. Although the active ingredient is terlipressin, the drug substance included in this product contains non-stoichiometric amounts of acetic acid and water, and this material is freely soluble in water. The structural formula of terlipressin is DESCRIPTION GLYPRESSIN is for intravenous injection. It consists of a clear, colourless liquid containing 0.85 mg terlipressin (equivalent to 1 mg terlipressin acetate) in 8.5 mL solution in an ampoule. The concentration of terlipressin is 0.1 mg/mL (equivalent to terlipressin acetate 0.12 mg/mL). List of excipients GLYPRESSIN contains the following excipients: Sodium chloride, acetic acid, sodium acetate trihydrate, Water for Injections PHARMACOLOGY Pharmacodynamics Terlipressin belongs to the pharmacotherapeutic group: Posterior pituitary lobe hormones (vasopressin and analogues), ATC code: H 01 BA 04. Terlipressin is a dodecapeptide that has three glycyl residues attached to the N-terminal of lysine vasopressin (LVP). Terlipressin acts as a pro-drug and is converted via enzymatic cleavage of its three glycyl residues to the biologically active lysine vasopressin. A large body of evidence has consistently shown that terlipressin given at doses of 0.85 mg and 1.7 mg respectively (equivalent to terlipressin acetate 1 mg and 2 mg respectively) can effectively reduce the portal venous pressure and produces marked vasoconstriction. -
Spray Desmopressin Acetate Nasal Spray 10 Μg/Spray
PRODUCT MONOGRAPH Pr DDAVP® Spray Desmopressin Acetate Nasal Spray 10 µg/spray Pr DDAVP® Rhinyle Desmopressin Acetate Nasal Solution 0.1 mg/mL Antidiuretic Ferring Inc. Date of Revision: 200 Yorkland Blvd, Suite 800 June 19, 2008 North York, Ontario M2J 5C1 Submission Control No: 119073 DDAVP® Spray and Rhinyle Page 1 of 23 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION.........................................................3 SUMMARY PRODUCT INFORMATION ........................................................................3 INDICATIONS AND CLINICAL USE..............................................................................3 WARNINGS AND PRECAUTIONS..................................................................................4 ADVERSE REACTIONS....................................................................................................6 DRUG INTERACTIONS ....................................................................................................7 DOSAGE AND ADMINISTRATION................................................................................7 OVERDOSAGE ..................................................................................................................9 ACTION AND CLINICAL PHARMACOLOGY ..............................................................9 STORAGE AND STABILITY..........................................................................................11 DOSAGE FORMS, COMPOSITION AND PACKAGING .............................................11 PART II: SCIENTIFIC INFORMATION -
Oxytocin Regulates the Expression of Aquaporin 5 in the Latepregnant Rat
RESEARCH ARTICLE Molecular Reproduction & Development 81:524–530 (2014) Oxytocin Regulates the Expression of Aquaporin 5 in the Late-Pregnant Rat Uterus ESZTER DUCZA,* ADRIENN B. SERES, JUDIT HAJAGOS-TOTH, GEORGE FALKAY, AND ROBERT GASPAR Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary SUMMARY Aquaporins (AQPs) are integral membrane channels responsible for the transport of water across a cell membrane. Based on reports that AQPs are present and accumulate in the female reproductive tract late in pregnancy, our aim was to study the expression of AQP isoforms (AQP1, 2, 3, 5, 8, and 9) at the end of pregnancy in rat in order to determine if they play a role in parturition. Reverse-transcriptase PCR revealed that specific Aqp mRNAs were detectable in the myometrium of non- pregnant and late-pregnancy (Days 18, 20, 21, and 22 of pregnancy) rat uteri. The expression of Aqp5 mRNA and protein were most pronounced on Days 18À21, and were dramatically decreased on Day 22 of pregnancy. In contrast, a significant increase was found in the level of Aqp5 transcript in whole-blood samples ÃCorresponding author: on the last day of pregnancy.The effect of oxytocin on myometrial Aqp5 expression in Department of Pharmacodynamics an organ bath was also investigated. The level of Aqp5 mRNA significantly decreased and Biopharmacy À8 University of Szeged, H-6720 5 min after oxytocin (10 M) administration, similarly to its profile on the day of Eotv€ os€ u. 6, Szeged 6270 delivery; this effect was sensitive to the oxytocin antagonist atosiban. The vasopres- Hungary. -
Management and Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus
REVIEW Management and treatment of lithium- induced nephrogenic diabetes insipidus Christopher K Finch†, Lithium carbonate is a well documented cause of nephrogenic diabetes insipidus, with as Tyson WA Brooks, many as 10 to 15% of patients taking lithium developing this condition. Clinicians have Peggy Yam & Kristi W Kelley been well aware of lithium toxicity for many years; however, the treatment of this drug- induced condition has generally been remedied by discontinuation of the medication or a †Author for correspondence Methodist University reduction in dose. For those patients unresponsive to traditional treatment measures, Hospital, Department several pharmacotherapeutic regimens have been documented as being effective for the of Pharmacy, University of management of lithium-induced diabetes insipidus including hydrochlorothiazide, Tennessee, College of Pharmacy, 1265 Union Ave., amiloride, indomethacin, desmopressin and correction of serum lithium levels. Memphis, TN 38104, USA Tel.: +1 901 516 2954 Fax: +1 901 516 8178 [email protected] Lithium carbonate is well known for its wide use associated with a mutation(s) of vasopressin in bipolar disorders due to its mood stabilizing receptors. Acquired causes are tubulointerstitial properties. It is also employed in aggression dis- disease (e.g., sickle cell disease, amyloidosis, orders, post-traumatic stress disorders, conduct obstructive uropathy), electrolyte disorders (e.g., disorders and even as adjunctive therapy in hypokalemia and hypercalcemia), pregnancy, or depression. Lithium has many well documented conditions induced by a drug (e.g., lithium, adverse effects as well as a relatively narrow ther- demeclocycline, amphotericin B and apeutic range of 0.4 to 0.8 mmol/l. Clinically vincristine) [3,4]. Lithium is the most common significant adverse effects include polyuria, mus- cause of drug-induced nephrogenic DI [5]. -
Vasopressin V2 Is a Promiscuous G Protein-Coupled Receptor That Is Biased by Its Peptide Ligands
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.28.427950; this version posted January 28, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Vasopressin V2 is a promiscuous G protein-coupled receptor that is biased by its peptide ligands. Franziska M. Heydenreich1,2,3*, Bianca Plouffe2,4, Aurélien Rizk1, Dalibor Milić1,5, Joris Zhou2, Billy Breton2, Christian Le Gouill2, Asuka Inoue6, Michel Bouvier2,* and Dmitry B. Veprintsev1,7,8,* 1Laboratory of Biomolecular Research, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland and Department of Biology, ETH Zürich, 8093 Zürich, Switzerland 2Department of Biochemistry and Molecular medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada 3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA 4The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, United Kingdom 5Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus-Vienna-Biocenter 5, 1030 Vienna, Austria 6Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan. 7Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, UK. 8Division of Physiology, Pharmacology & Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK. *Correspondence should be addressed to: [email protected], [email protected], [email protected]. -
Molecular Basis of Ligand Recognition and Activation of Human V2 Vasopressin Receptor
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.18.427077; this version posted January 18, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Molecular basis of ligand recognition and activation of human V2 vasopressin receptor Fulai Zhou1, 12, Chenyu Ye2, 12, Xiaomin Ma3, 12, Wanchao Yin1, Qingtong Zhou4, Xinheng He1, 5, Xiaokang Zhang6, 7, Tristan I. Croll8, Dehua Yang1, 5, 9, Peiyi Wang3, 10, H. Eric Xu1, 5, 11, Ming-Wei Wang1, 2, 4, 5, 9, 11, Yi Jiang1, 5, 1. The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China 2. School of Pharmacy, Fudan University, Shanghai 201203, China 3. Cryo-EM Centre, Southern University of Science and Technology, Shenzhen 515055, China 4. School of Basic Medical Sciences, Fudan University, Shanghai 200032, China 5. University of Chinese Academy of Sciences, 100049 Beijing, China 6. Interdisciplinary Center for Brain Information, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; 7. Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China 8. Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, UK 9. The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203 Shanghai, China 10. Department of Biology, Southern University of Science and Technology, Shenzhen 515055, China 11. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China 12. These authors contributed equally: Fulai Zhou, Chenyu Ye, and Xiaomin Ma. -
Oral Desmopressin in Central Diabetes Insipidus
Arch Dis Child: first published as 10.1136/adc.61.3.247 on 1 March 1986. Downloaded from Archives of Disease in Childhood, 1986, 61, 247-250 Oral desmopressin in central diabetes insipidus U WESTGREN, C WITTSTROM, AND A S HARRIS Department of Pediatrics, University Hospital, Lund, and Faculty of Pharmacy, Biomedicum, Uppsala, Sweden SUMMARY Seven paediatric patients with central diabetes insipidus were studied in an open dose ranging study in hospital followed by a six month study on an outpatient basis to assess the efficacy and safety of peroral administration of DDAVP (desmopressin) tablets. In the dose ranging study a dose dependent antidiuretic response was observed. The response to 12-5-50 mcg was, however, less effective in correcting baseline polyuria than were doses of 100 mcg and above. Patients were discharged from hospital on a preliminary dosage regimen ranging from 100 to 400 mcg three times daily. After an initial adjustment in dosage in three patients at one week follow up, all patients were stabilised on treatment with tablets and reported an adequate water turnover at six months. As with the intranasal route of administration dosage requirements varied from patient to patient, and a dose range rather than standard doses were required. A significant correlation, however, was found for the relation between previous intranasal and present oral daily dosage. No adver-se reactions were reported. No clinically significant changes were noted in blood chemistry and urinalysis. All patients expressed a preference for the oral over existing intranasal copyright. treatment. Treatment with tablets offers a beneficial alternative to the intranasal route, particularly in patients with chronic rhinitis or impaired vision. -
Tractocile, Atosiban
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Tractocile 6.75 mg/0.9 ml solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each vial of 0.9 ml solution contains 6.75 mg atosiban (as acetate). For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection). Clear, colourless solution without particles. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Tractocile is indicated to delay imminent pre-term birth in pregnant adult women with: regular uterine contractions of at least 30 seconds duration at a rate of 4 per 30 minutes a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of 50% a gestational age from 24 until 33 completed weeks a normal foetal heart rate 4.2 Posology and method of administration Posology Treatment with Tractocile should be initiated and maintained by a physician experienced in the treatment of pre-term labour. Tractocile is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with Tractocile 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of Tractocile 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of Tractocile 37.5 mg/5 ml concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The duration of the treatment should not exceed 48 hours. The total dose given during a full course of Tractocile therapy should preferably not exceed 330.75 mg of atosiban. -
Largescale Synthesis of Peptides
Lars Andersson1 Lennart Blomberg1 Large-Scale Synthesis of Martin Flegel2 Ludek Lepsa2 Peptides Bo Nilsson1 Michael Verlander3 1 PolyPeptide Laboratories (Sweden) AB, Malmo, Sweden 2 PolyPeptide Laboratories SpoL, Prague, Czech Republic 3 PolyPeptide Laboratories, Inc., Torrance, CA, 90503 USA Abstract: Recent advances in the areas of formulation and delivery have rekindled the interest of the pharmaceutical community in peptides as drug candidates, which, in turn, has provided a challenge to the peptide industry to develop efficient methods for the manufacture of relatively complex peptides on scales of up to metric tons per year. This article focuses on chemical synthesis approaches for peptides, and presents an overview of the methods available and in use currently, together with a discussion of scale-up strategies. Examples of the different methods are discussed, together with solutions to some specific problems encountered during scale-up development. Finally, an overview is presented of issues common to all manufacturing methods, i.e., methods used for the large-scale purification and isolation of final bulk products and regulatory considerations to be addressed during scale-up of processes to commercial levels. © 2000 John Wiley & Sons, Inc. Biopoly 55: 227–250, 2000 Keywords: peptide synthesis; peptides as drug candidates; manufacturing; scale-up strategies INTRODUCTION and plants,5 have all combined to increase the avail- ability and lower the cost of producing peptides. For For almost half a century, since du Vigneaud first many years, however, the major obstacle to the suc- presented his pioneering synthesis of oxytocin to the cess of peptides as pharmaceuticals was their lack of world in 1953,1 the pharmaceutical community has oral bioavailability and, therefore, relatively few pep- been excited about the potential of peptides as “Na- tides reached the marketplace as approved drugs. -
Vasopressin and Terlipressin in Adult Vasodilatory Shock: a Systematic Review and Meta-Analysis of Nine Randomized Controlled Tr
Serpa Neto et al. Critical Care 2012, 16:R154 http://ccforum.com/content/16/4/R154 RESEARCH Open Access Vasopressin and terlipressin in adult vasodilatory shock: a systematic review and meta-analysis of nine randomized controlled trials Ary Serpa Neto1*, Antônio P Nassar Júnior2, Sérgio O Cardoso1, José A Manetta1, Victor GM Pereira1, Daniel C Espósito1, Maria CT Damasceno1 and James A Russell3 Abstract Introduction: Catecholamines are the most used vasopressors in vasodilatory shock. However, the development of adrenergic hyposensitivity and the subsequent loss of catecholamine pressor activity necessitate the search for other options. Our aim was to evaluate the effects of vasopressin and its analog terlipressin compared with catecholamine infusion alone in vasodilatory shock. Methods: A systematic review and meta-analysis of publications between 1966 and 2011 was performed. The Medline and CENTRAL databases were searched for studies on vasopressin and terlipressin in critically ill patients. The meta-analysis was limited to randomized controlled trials evaluating the use of vasopressin and/or terlipressin compared with catecholamine in adult patients with vasodilatory shock. The assessed outcomes were: overall survival, changes in the hemodynamic and biochemical variables, a decrease of catecholamine requirements, and adverse events. Results: Nine trials covering 998 participants were included. A meta-analysis using a fixed-effect model showed a reduction in norepinephrine requirement among patients receiving terlipressin or vasopressin infusion compared with control (standardized mean difference, -1.58 (95% confidence interval, -1.73 to -1.44); P < 0.0001). Overall, vasopressin and terlipressin, as compared with norepinephrine, reduced mortality (relative risk (RR), 0.87 (0.77 to 0.99); P = 0.04).