DOCSLIB.ORG

Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration. See “FDA Briefing Document: Pharmacy Compounding Advisory Committee (PCAC) Meeting (March 8 and 9, 2016),” available at https://www.regulations.gov/document/FDA-2018-N-3240-0285. 3 See https://www.fda.gov/drugs/human-drug-compounding/safety-risks-associated-certain-bulk-drug-substances- nominated-use-compounding. 1 Updated June 07, 2021 503B Category 1: Bulk Drug Substances Under Evaluati on ** Designates bulk drug substances that are components of FDA approved drugs4 • 5-Methyltetrahydrofolate Calcium • Brompheniramine maleate, USP** • 17-alpha-Hydroxyprogesterone • Budesonide** • Acetylcysteine** • Bumetanide** • Acyclovir** • Bupivacaine Hydrochloride** • Adapalene** • Caffeine** • Adenosine** • Calcipotriene** • Allantoin • Calcium Chloride** • Alpha Lipoic Acid • Calcium Gluconate** • Alprostadil** • Cantharidin • Aluminum Chloride Hexahydrate • Chloroquine Phosphate** • Aluminum potassium sulfate • Chlorpheniramine Maleate** • Amantadine Hydrochloride** • Choline Chloride • Amitriptyline Hydrochloride** • Chromic Chloride** • Amphotericin B** • Chromium Chloride** • Anastrazole** • Ciclopirox Olamine** • Arginine Hydrochloride/L-arginine • Cimetidine** Hydrochloride** • Ciprofloxacin Hydrochloride** • Ascorbic acid** • Citric Acid Anhydrous** • Ascorbyl Palmitate • Citrulline/L-Citrulline • Aspartic Acid • Clindamycin Phosphate** • Atenolol** • Clioquinol** • Atropine sulfate** • Clobetasol Propionate** • Azelaic Acid** • Clomipramine Hydrochloride** • Baclofen** • Clonidine Hydrochloride** • Benzocaine • Coal Tar Solution • Betahistine Hydrochloride • Cocaine Hydrochloride** • Betamethasone Acetate** • Copper Gluconate • Betamethasone Dipropionate** • Cupric Sulfate** • Betamethasone Sodium Phosphate** • Cyanocobalamin** • Biotin** • Cyclobenzaprine Hydrochloride** • Bismuth Nitrate Oxide • Cyclosporine/Cyclosporine A** • Brilliant Blue • Dapiprazole Hydrochloride** • Brimonidine Tartrate** • Dapsone** • Bromfenac sodium (for ophthalmic • Desoximetasone** solutions only) ** • Dexamethasone Acetate 4 A condition of section 503B of the FD&C Act is that the compounded drug product is not essentially a copy of one or more approved drug products. For more information about the “essentially a copy” provision in section 503B, see FDA’s guidance for industry “Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act.” In addition, FDA does not intend to take action against an outsourcing facility for failing to compound in accordance with section 503B(a)(5) if it fills orders for a compounded drug that is essentially a copy of an approved drug that has been discontinued and is no longer marketed. Bulk drug substances in Category 1 that are components of FDA-approved drugs are designated with two asterisks (**) below. 2 Updated June 07, 2021 • Dexamethasone Sodium Phosphate** • Glutamine** • Dexpanthenol** • Glutathione • DHEA (dehydroepiandrosterone) ** • Glycerin** • D-glucose** • Glycolic Acid • Diazepam** • Glycopyrrolate/ Glycopyrrolate • Dibucaine Hydrochloride** Bromide** • Diclofenac Sodium** • Haloperidol** • Diiodohyroxyquinolone • Heparin sodium** • Diltiazem Hydrochloride** • Hyaluronic acid sodium salt • Dimercapto-1-propanesulfonic acid • Hydralazine Hydrochloride** (DMPS)** • Hydrochloric Acid • Diphenhydramine Hydrochloride** • Hydrocortisone** • Diphenylcyclopropenone • Hydromorphone Hydrochloride** • Dipyridamole** • Hydroquinone** • Disulfiram** • Hydroxocobalamin Hydrochloride • Dobutamine Hydrochloride** • Hydroxychloroquine Sulfate** • Dopamine Hydrochloride** • Hydroxyzine Hydrochloride** • Droperidol** Ibuprofen** • Dyclonine Hydrochloride** • Ibutamoren Mesylate • Econazole Nitrate** • Imipramine Hydrochloride** • Edetate Calcium Disodium** • Imiquimod** • Edetate Disodium • Inositol • Ephedrine Hydrochloride • Iodoform • Ephedrine sulfate, USP** • Itraconazole** • Epinephrine** • Ivermectin** • Epinephrine Bitartrate** • Ketamine Hydrochloride** • Estradiol Cypionate** • Ketoconazole** • Estradiol** • Ketoprofen** • Estriol • Ketorolac Tromethamine** • Estrone** • Labetalol Hydrochloride** • Ethanol** • Lactic Acid** • Ethyl Aminobenzoate • Lansoprazole** • Etomidate** • Levocetirizine Dihydrochloride** • Famotidine** • Lidocaine Hydrochloride** • Fentanyl Citrate** • Lincomycin Hydrochloride** • Finasteride** • L-Lysine • Fluconazole** • L-lysine Hydrochloride/Lysine • Fluocinolone Acetonide** Hydrochloride • Fluocinonide** • Lorazepam** • Flurbiprofen** • L-Proline • Fluticasone Propionate** • Magnesium Chloride ** • Folic Acid** • Magnesium Sulfate ** • Formaldehyde • Malic Acid • Furosemide** • Manganese Chloride** • Gabapentin** • Manganese Sulfate ** • Gentamicin Sulfate** • Mannitol** • Glucosamine Sulfate Potassium Chloride • Medroxyprogesterone Acetate** • Glucosamine Sulfate Sodium Chloride • Meperidine Hydrochloride (a.k.a. • Glutamic acid** Pethidine Hydrochloride)** 3 Updated June 07, 2021 • Methacholine Chloride** • Precipitated Sulfur • Methionine/ Methionine (L) • Prednisolone** • Methylcobalamin/Methyl B12 • Prednisolone Acetate** • Methylprednisolone Acetate** • Prilocaine** • Methylsulfonylmethane (MSM) • Procainamide Hydrochloride** • Metoclopramide Hydrochloride ** • Procaine Hydrochloride** • Metronidazole** • Progesterone** • Midazolam Hydrochloride** • Promethazine Hydrochloride** • Mineral Oil** • Proparacaine Hydrochloride** • Minoxidil** • Propranolol hydrochloride** • Mitomycin** • Prostaglandin E1** • Mometasone Furoate** • Pyridoxal 5-Phosphate Monohydrate • Monosodium Glutamate • Pyridoxine Hydrochloride** • Morphine Sulfate ** • Quinacrine Hydrochloride (except for • Moxifloxacin hydrochloride** intrauterine administration) • Mupirocin** • Remifentanil Hydrochloride** • Nalbuphine Hydrochloride** • Riboflavin Sodium Phosphate ** • Naloxone Hydrochloride Dihydrate** • Rocuronium Bromide** • Nandrolone Decanoate** • Ropivacaine Hydrochloride** • Neomycin sulfate** • Salicylic Acid • Neostigmine Methylsulfate** • Scopolamine hydrobromide • Nepafenac** • Sermorelin Acetate** • Niacin** • Sincalide ** • Niacinamide** • Sodium Acetate Anhydrous** • Nifedipine** • Sodium Ascorbate** • Norepinephrine Bitartrate** • Sodium Benzoate** • Ondansetron Hydrochloride** • Sodium Bicarbonate** • Ornithine Hydrochloride • Sodium Chloride** • Oxymetazoline Hydrochloride** • Sodium Citrate** • Oxytocin** • Sodium L-Aspartate Monohydrate • Papaverine Hydrochloride • Sodium Molybdate • Pentoxifylline** • Sodium Nitroprusside ** • Phenol • Sodium phosphate/ Sodium Phosphate • Phenoxybenzamine Hydrochloride** Monobasic** • Phentolamine Mesylate** • Sodium Selenite • Phenylephrine Hydrochloride** • Sodium Tetradecyl Sulfate** • Phosphatidylcholine • Sodium thiosulfate** • Phytonadione** • Spironolactone** • Pitcher Plant • Squaric acid dibutyl ester • Podophyllum/Podophyllum Resin • Succinylcholine Chloride** • Polidocanol** • Sufentanil Citrate** • Polymyxin B Sulfate** • Sulfacetamide Sodium Monohydrate** • Potassium Acetate** • Sulfan Blue • Potassium chloride** • Tacrolimus** • Potassium Phosphate Monobasic • Taurine [KH2PO4]** • Tazarotene** • Potassium Phosphate Dibasic [K2HPO4]/ • Terbinafine Hydrochloride** Potassium Phosphate Dibasic • Testosterone** Anhydrous** • Testosterone Cypionate** 4 Updated June 07, 2021 • Testosterone Propionate** • Trypan Blue** • Tetracaine Hydrochloride** • Ubidecarenone (Coenzyme Q10) • Tetracycline Hydrochloride** • Urea** • Theophylline** • Vancomycin Hydrochloride** • Thiamine Hydrochloride
Load more

Recommended publications
  • CCA One Care Options Formulary
    Commonwealth Care Alliance One Care Plan (Medicare-Medicaid Plan) 2021 List of Covered Drugs (Formulary) 30 Winter Street • Boston, MA 02108 PLEASE READ: THIS DOCUMENT CONTAINS INFORMATION ABOUT THE DRUGS WE COVER IN THIS PLAN For more recent information or other questions, contact Commonwealth Care Alliance Member Services at 1-866-610-2273 (TTY: call MassRelay at 711), 8 a.m. – 8 p.m., 7 days a week, or visit www.commonwealthonecare.org H0137_CF2021 Approved Formulary: ID 00021588 • Version 13 • Updated on 08/01/2021 One Care Plan | 2021 List of Covered Drugs (Formulary) Introduction This document is called the List of Covered Drugs (also known as the Drug List). It tells you which prescription drugs, over-the-counter drugs and items are covered by Commonwealth Care Alliance. The Drug List also tells you if there are any special rules or restrictions on any drugs covered by One Care. Key terms and their definitions appear in the last chapter of the Member Handbook. Table of Contents A. Disclaimers ........................................................................................................................ 4 B. Frequently Asked Questions (FAQ) .................................................................................. 5 What prescription drugs are on the List of Covered Drugs? (We call the List of Covered Drugs the “Drug List” for short.) ................................................................... 5 B2. Does the Drug List ever change? ............................................................................... 5 B3. What happens when there is a change to the Drug List? ........................................... 6 B4. Are there any restrictions or limits on drug coverage or any required actions to take to get certain drugs? .................................................................................................. 7 B5. How will you know if the drug you want has limitations or if there are required actions to take to get the drug? .................................................................................
    [Show full text]
  • Azelaic Acid
    Azelaic Acid (FINACEA) Topical Foam 15% National Drug Monograph August 2016 VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives The purpose of VA PBM Services drug monographs is to provide a focused drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information Description/Mechanism of Azelaic acid is a naturally occurring C9-dicarboxylic acid that is found in plants Action (such as whole grain cereals), animals and humans. Azelaic acid has antiinflammatory, antioxidative and antikeratinizing effects. In rosacea skin, azelaic acid decreases cathelicidin levels and kallikrein 5 (KLK5) activity and possibly inhibits toll-like receptor 2 (TLR2) expression.1 A 15% gel formulation has been marketed for rosacea, and 20% cream has been available for acne vulgaris. The newer foam formulation consists of an oil- in-water emulsion and was designed to have a higher lipid content than the gel for dry and sensitive skin. Indication(s) Under Review Topical treatment of inflammatory papules and pustules of mild to moderate in This Document rosacea. Dosage Form(s) Under Foam, 15% Review REMS REMS No REMS Postmarketing Requirements See Other Considerations for additional REMS information Pregnancy Rating Category B Executive Summary Efficacy There have been no head-to-head trials comparing the foam and gel formulations of azelaic acid in terms of safety, tolerability and efficacy in the treatment of papulopustular (PP) rosacea.. In two major randomized clinical trials, azelaic acid foam produced small benefits over vehicle foam in achieving Investigator’s Global Assessment (IGA) treatment success (NNTs of 9.2 and 11.5) and in reducing inflammatory lesion counts.
    [Show full text]
  • Betamethasone
    Betamethasone Background Betamethasone is a potent, long-acting, synthetic glucocorticoid widely used in equine veterinary medicine as a steroidal anti-inflammatory.1 It is often administered intra-articularly for control of pain associated with inflammation and osteoarthritis.2 Betamethasone is a prescription medication and can only be dispensed from or upon the request of a http://en.wikipedia.org/wiki/Betamethasone#/media/File:Betamethasone veterinarian. It is commercially available .png in a variety of formulations including BetaVet™, BetaVet Soluspan Suspension® and Betasone Aqueous Suspension™.3 Betamethasone can be used intra-articularly, intramuscularly, by inhalation, and topically.4 When administered intra-articularly, it is often combined with other substances such as hyaluronan.5 Intra-articular and intramuscular dosages range widely based upon articular space, medication combination protocol, and practitioner preference. Betamethasone is a glucocorticoid receptor agonist which binds to various glucocorticoid receptors setting off a sequence of events affecting gene transcription and the synthesis of proteins. These mechanisms of action include: • Potential alteration of the G protein-coupled receptors to interfere with intracellular signal transduction pathways • Enhanced transcription in many genes, especially those involving suppression of inflammation. • Inhibition of gene transcription – including those that encode pro-inflammatory substances. The last two of these are considered genomic effects. This type of corticosteroid effect usually occurs within hours to days after administration. The genomic effects persist after the concentrations of the synthetic corticosteroid in plasma are no longer detectable, as evidenced by persistent suppression of the normal production of hydrocortisone following synthetic corticosteroid administration.6 When used judiciously, corticosteroids can be beneficial to the horse.
    [Show full text]
  • The National Drugs List
    ^ ^ ^ ^ ^[ ^ The National Drugs List Of Syrian Arab Republic Sexth Edition 2006 ! " # "$ % &'() " # * +$, -. / & 0 /+12 3 4" 5 "$ . "$ 67"5,) 0 " /! !2 4? @ % 88 9 3: " # "$ ;+<=2 – G# H H2 I) – 6( – 65 : A B C "5 : , D )* . J!* HK"3 H"$ T ) 4 B K<) +$ LMA N O 3 4P<B &Q / RS ) H< C4VH /430 / 1988 V W* < C A GQ ") 4V / 1000 / C4VH /820 / 2001 V XX K<# C ,V /500 / 1992 V "!X V /946 / 2004 V Z < C V /914 / 2003 V ) < ] +$, [2 / ,) @# @ S%Q2 J"= [ &<\ @ +$ LMA 1 O \ . S X '( ^ & M_ `AB @ &' 3 4" + @ V= 4 )\ " : N " # "$ 6 ) G" 3Q + a C G /<"B d3: C K7 e , fM 4 Q b"$ " < $\ c"7: 5) G . HHH3Q J # Hg ' V"h 6< G* H5 !" # $%" & $' ,* ( )* + 2 ا اوا ادو +% 5 j 2 i1 6 B J' 6<X " 6"[ i2 "$ "< * i3 10 6 i4 11 6! ^ i5 13 6<X "!# * i6 15 7 G!, 6 - k 24"$d dl ?K V *4V h 63[46 ' i8 19 Adl 20 "( 2 i9 20 G Q) 6 i10 20 a 6 m[, 6 i11 21 ?K V $n i12 21 "% * i13 23 b+ 6 i14 23 oe C * i15 24 !, 2 6\ i16 25 C V pq * i17 26 ( S 6) 1, ++ &"r i19 3 +% 27 G 6 ""% i19 28 ^ Ks 2 i20 31 % Ks 2 i21 32 s * i22 35 " " * i23 37 "$ * i24 38 6" i25 39 V t h Gu* v!* 2 i26 39 ( 2 i27 40 B w< Ks 2 i28 40 d C &"r i29 42 "' 6 i30 42 " * i31 42 ":< * i32 5 ./ 0" -33 4 : ANAESTHETICS $ 1 2 -1 :GENERAL ANAESTHETICS AND OXYGEN 4 $1 2 2- ATRACURIUM BESYLATE DROPERIDOL ETHER FENTANYL HALOTHANE ISOFLURANE KETAMINE HCL NITROUS OXIDE OXYGEN PROPOFOL REMIFENTANIL SEVOFLURANE SUFENTANIL THIOPENTAL :LOCAL ANAESTHETICS !67$1 2 -5 AMYLEINE HCL=AMYLOCAINE ARTICAINE BENZOCAINE BUPIVACAINE CINCHOCAINE LIDOCAINE MEPIVACAINE OXETHAZAINE PRAMOXINE PRILOCAINE PREOPERATIVE MEDICATION & SEDATION FOR 9*: ;< " 2 -8 : : SHORT -TERM PROCEDURES ATROPINE DIAZEPAM INJ.
    [Show full text]
  • Acesulfame Potassium
    ACESULFAME POTASSIUM Prepared at the 57th JECFA (2001) and published in FNP 52 Add 9 (2001), superseding specifications prepared at the 46th JECFA (1996) and published in FNP 52 Add 4 (1996). An ADI of 0-15 mg/kg body weight was established at the 37th JECFA (1990). SYNONYMS Acesulfame K; INS No. 950 DEFINITION Chemical names Potassium salt of 6-methyl-1,2,3-oxathiazine-4(3H)-one-2,2-dioxide; potassium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide C.A.S. number 55589-62-3 Chemical formula C4H4KNO4S Structural formula Formula weight 201.24 Assay Not less than 99.0% and not more than 101.0% on the dried basis DESCRIPTION Odourless, white crystalline powder FUNCTIONAL USES Sweetener, flavour enhancer CHARACTERISTICS IDENTIFICATION Solubility (Vol. 4) Freely soluble in water, very slightly soluble in ethanol Spectrophotometry Dissolve 10 mg of the sample in 1,000 ml of water. The solution shows an absorbance maximum at 227±2 nm Test for potassium Passes test (Vol.4) Test the residue obtained by igniting 2 g of the sample Precipitation test Add a few drops of a 10% solution of sodium cobaltinitrite to a solution of 0.2 g of the sample in 2 ml of acetic acid TS and 2 ml of water. A yellow precipitate is produced. PURITY Loss on drying (Vol. 4) Not more than 1.0% (105o, 2 h) pH (Vol. 4) 5.5 - 7.5 (1% soln) Organic impurities Passes test for 20 mg/kg of UV active components See description under TESTS Fluoride (Vol.
    [Show full text]
  • The Detection and Determination of Esters
    Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1958 The etD ection and Determination of Esters. Mohd. Mohsin Qureshi Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Qureshi, Mohd. Mohsin, "The eD tection and Determination of Esters." (1958). LSU Historical Dissertations and Theses. 501. https://digitalcommons.lsu.edu/gradschool_disstheses/501 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. Copright by Mohcl Mohsin Qureshi 1959 THE DETECTION AND DETERMINATION OF ESTERS A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in The Department of Chemistry by Mohd. Mohsin Qureshi M.Sc., Aligarh University, 1944 August, 1958 ACKNOWLEDGMENT The author wishes to express his sincere apprecia­ tion and gratitude to Dr. Philip W. West under whose guidance this research was carried out. He is grateful to Dr. James G. Traynham for sup­ plying him with a number of esters and for his many helpful suggestions. The financial support given to him by the Continental Oil Company is gratefully acknowledged. He offers his sincere thanks to Miss Magdalena Usategul for her valuable suggestions and her ungrudging help during the course of this investigation. Dr. Anil K.
    [Show full text]
  • Hygroscopicity of Pharmaceutical Crystals
    HYGROSCOPICITY OF PHARMACEUTICAL CRYSTALS A DISSERTATION SUBMITTED TO THE FACULTY OF GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY DABING CHEN IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY RAJ SURYANARAYANAN (ADVISER) JANUARY, 2009 © Dabing Chen, January / 2009 ACKNOWLEDGEMENTS I am very grateful to my thesis advisor, Prof. Raj Suryanarayanan, for his constant guidance, support, and encouragement throughout my research. Without his help, the completion of this thesis would be impossible. His friendship and advices are precious to my professional and personal growth and will help me overcome many difficulties in my future career. I would like to take the opportunity to thank Prof. David J.W. Grant, who was my advisor during the first three years in graduate school and led me into the research area of physical pharmacy. It was my great honor to have worked for him, and he will always live as a role model in my life. Many thanks to Dr. Zheng Jane Li at Boehringer Ingelheim Pharmaceuticals (BI) for her invaluable advice as an industrial mentor and also for agreeing to serve on my committee. I sincerely appreciate her helpful discussions, revision of the manuscripts, and supervision of my research. I also want to thank her for providing me the internship opportunity at BI. I thank Dr. Timothy S. Wiedmann and Dr. Theodore P. Labuza for serving on my committee and for critically reviewing my thesis. I also want to thank Dr. Timothy S. Wiedmann for allowing me the use of the HPLC instruments in his lab and also for his advice as the Director of Graduate Studies.
    [Show full text]
  • Acetadote (Acetylcysteine) Injection Is Available As a 20% Solution in 30 Ml (200Mg/Ml) Single Dose Glass Vials
    NDA 21-539/S-004 Page 3 Acetadote® (acetylcysteine) Injection Package Insert NDA 21-539/S-004 Page 4 RX ONLY PRESCRIBING INFORMATION ACETADOTE® (acetylcysteine) Injection For Intravenous Use DESCRIPTION Acetylcysteine injection is an intravenous (I.V.) medication for the treatment of acetaminophen overdose. Acetylcysteine is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine (N-acetyl-L-cysteine, NAC). The compound is a white crystalline powder, which melts in the range of 104° to 110°C and has a very slight odor. The molecular formula of the compound is C5H9NO3S, and its molecular weight is 163.2. Acetylcysteine has the following structural formula: H CH3 N SH O COOH Acetadote is supplied as a sterile solution in vials containing 20% w/v (200 mg/mL) acetylcysteine. The pH of the solution ranges from 6.0 to 7.5. Acetadote contains the following inactive ingredients: 0.5 mg/mL disodium edetate, sodium hydroxide (used for pH adjustment), and Sterile Water for Injection, USP. CLINICAL PHARMACOLOGY Acetaminophen Overdose: Acetaminophen is absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. It is extensively metabolized in the liver to form principally the sulfate and glucoronide conjugates which are excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by isozyme CYP2E1 of the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite. The toxic metabolite preferentially conjugates with hepatic glutathione to form nontoxic cysteine and mercapturic acid derivatives, which are then excreted by the kidney.
    [Show full text]
  • The Promise of N-Acetylcysteine in Neuropsychiatry
    Review The promise of N-acetylcysteine in neuropsychiatry 1,2,3,4 5,6 1 1,2,4 Michael Berk , Gin S. Malhi , Laura J. Gray , and Olivia M. Dean 1 School of Medicine, Deakin University, Geelong, Victoria, Australia 2 Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia 3 Orygen Research Centre, Parkville, Victoria, Australia 4 The Florey Institute of Neuroscience and Mental Health, Victoria, Australia 5 Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia 6 CADE Clinic, Department of Psychiatry, Level 5 Building 36, Royal North Shore Hospital, St Leonards, 2065, Australia N-Acetylcysteine (NAC) targets a diverse array of factors with the pathophysiology of a diverse range of neuropsy- germane to the pathophysiology of multiple neuropsy- chiatric disorders, including autism, addiction, depression, chiatric disorders including glutamatergic transmission, schizophrenia, bipolar disorder, and Alzheimer’s and Par- the antioxidant glutathione, neurotrophins, apoptosis, kinson’s diseases [3]. Determining precisely how NAC mitochondrial function, and inflammatory pathways. works is crucial both to understanding the core biology This review summarises the areas where the mecha- of these illnesses, and to opening the door to other adjunc- nisms of action of NAC overlap with known pathophysi- tive therapies operating on these pathways. The current ological elements, and offers a pre´ cis of current literature article will initially review the possible mechanisms of regarding the use of NAC in disorders including cocaine, action of NAC, and then critically appraise the evidence cannabis, and smoking addictions, Alzheimer’s and Par- that suggests it has efficacy in the treatment of neuropsy- kinson’s diseases, autism, compulsive and grooming chiatric disorders.
    [Show full text]
  • Brimonidine Tartrate; Brinzolamide
    Contains Nonbinding Recommendations Draft Guidance on Brimonidine Tartrate ; Brinzolamide This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the Office of Generic Drugs. Active Ingredient: Brimonidine tartrate; Brinzolamide Dosage Form; Route: Suspension/drops; ophthalmic Strength: 0.2%; 1% Recommended Studies: One study Type of study: Bioequivalence (BE) study with clinical endpoint Design: Randomized (1:1), double-masked, parallel, two-arm, in vivo Strength: 0.2%; 1% Subjects: Males and females with chronic open angle glaucoma or ocular hypertension in both eyes. Additional comments: Specific recommendations are provided below. ______________________________________________________________________________ Analytes to measure (in appropriate biological fluid): Not applicable Bioequivalence based on (95% CI): Clinical endpoint Additional comments regarding the BE study with clinical endpoint: 1. The Office of Generic Drugs (OGD) recommends conducting a BE study with a clinical endpoint in the treatment of open angle glaucoma and ocular hypertension comparing the test product to the reference listed drug (RLD), each applied as one drop in both eyes three times daily at approximately 8:00 a.m., 4:00 p.m., and 10:00 p.m. for 42 days (6 weeks). 2. Inclusion criteria (the sponsor may add additional criteria): a. Male or nonpregnant females aged at least 18 years with chronic open angle glaucoma or ocular hypertension in both eyes b.
    [Show full text]
  • Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development
    processes Review Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development Outi M. H. Salo-Ahen 1,2,* , Ida Alanko 1,2, Rajendra Bhadane 1,2 , Alexandre M. J. J. Bonvin 3,* , Rodrigo Vargas Honorato 3, Shakhawath Hossain 4 , André H. Juffer 5 , Aleksei Kabedev 4, Maija Lahtela-Kakkonen 6, Anders Støttrup Larsen 7, Eveline Lescrinier 8 , Parthiban Marimuthu 1,2 , Muhammad Usman Mirza 8 , Ghulam Mustafa 9, Ariane Nunes-Alves 10,11,* , Tatu Pantsar 6,12, Atefeh Saadabadi 1,2 , Kalaimathy Singaravelu 13 and Michiel Vanmeert 8 1 Pharmaceutical Sciences Laboratory (Pharmacy), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland; ida.alanko@abo.fi (I.A.); rajendra.bhadane@abo.fi (R.B.); parthiban.marimuthu@abo.fi (P.M.); atefeh.saadabadi@abo.fi (A.S.) 2 Structural Bioinformatics Laboratory (Biochemistry), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland 3 Faculty of Science-Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands; [email protected] 4 Swedish Drug Delivery Forum (SDDF), Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; [email protected] (S.H.); [email protected] (A.K.) 5 Biocenter Oulu & Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7 A, FI-90014 Oulu, Finland; andre.juffer@oulu.fi 6 School of Pharmacy, University of Eastern Finland, FI-70210 Kuopio, Finland; maija.lahtela-kakkonen@uef.fi (M.L.-K.); tatu.pantsar@uef.fi
    [Show full text]
  • Hormonal Responses to Non-Nutritive Sweeteners in Water and Diet Soda Allison C
    Sylvetsky et al. Nutrition & Metabolism (2016) 13:71 DOI 10.1186/s12986-016-0129-3 RESEARCH Open Access Hormonal responses to non-nutritive sweeteners in water and diet soda Allison C. Sylvetsky1,2,3, Rebecca J. Brown1, Jenny E. Blau1, Mary Walter4 and Kristina I. Rother1* Abstract Background: Non-nutritive sweeteners (NNS), especially in form of diet soda, have been linked to metabolic derangements (e.g. obesity and diabetes) in epidemiologic studies. We aimed to test acute metabolic effects of NNS in isolation (water or seltzer) and in diet sodas. Methods: We conducted a four-period, cross-over study at the National Institutes of Health Clinical Center (Bethesda, Maryland). Thirty healthy adults consumed 355 mL water with 0 mg, 68 mg, 170 mg, and 250 mg sucralose, and 31 individuals consumed 355 mL caffeine-free Diet Rite Cola™, Diet Mountain Dew™ (18 mg sucralose, 18 mg acesulfame-potassium, 57 mg aspartame), and seltzer water with NNS (68 mg sucralose and 41 mg acesulfame-potassium, equivalent to Diet Rite Cola™) in randomized order, prior to oral glucose tolerance tests. Blood samples were collected serially for 130 min. Measures included GLP-1, GIP, glucose, insulin, C-peptide, glucose absorption, gastric emptying, and subjective hunger and satiety ratings. Results: Diet sodas augmented active GLP-1 (Diet Rite Cola™ vs. seltzer water, AUC, p =0.039;DietMountainDew™ vs. seltzer water, AUC, p = 0.07), but gastric emptying and satiety were unaffected. Insulin concentrations were nominally higher following all NNS conditions without altering glycemia. Sucralose alone (at any concentration) did not affect metabolic outcomes. Conclusions: Diet sodas but not NNS in water augmented GLP-1 responses to oral glucose.
    [Show full text]