Formulations of Viable Cells for Oral Delivery

Total Page:16

File Type:pdf, Size:1020Kb

Formulations of Viable Cells for Oral Delivery (19) TZZ ¥_Z_T (11) EP 2 384 190 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/20 (2006.01) A61K 9/50 (2006.01) 26.07.2017 Bulletin 2017/30 A61K 35/74 (2015.01) (21) Application number: 10700756.9 (86) International application number: PCT/GB2010/000035 (22) Date of filing: 11.01.2010 (87) International publication number: WO 2010/079343 (15.07.2010 Gazette 2010/28) (54) FORMULATIONS OF VIABLE CELLS FOR ORAL DELIVERY FORMULIERUNGEN AUS LEBENSFÄHIGEN ZELLEN FÜR ORALE FREISETZUNG FORMULATIONS DE CELLULES VIABLES POUR UNE ADMINISTRATION ORALE (84) Designated Contracting States: WO-A1-2007/140613 WO-A2-2004/076657 AT BE BG CH CY CZ DE DK EE ES FI FR GB GR WO-A2-2007/079147 GB-A- 825 480 HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL US-A- 5 942 242 US-A1- 2006 093 591 PT RO SE SI SK SM TR • DATABASE WPI Section Ch, Week 200377 (30) Priority: 09.01.2009 GB 0900350 Thomson Scientific, London, GB; Class D13, AN 2003-820419 XP002587845 KAJIYA T; MORI H; (43) Date of publication of application: OKADA H; ONISHI H; SAWADA S; TAKAGI S; 09.11.2011 Bulletin 2011/45 TASHIROM: "Foodstuff containing Lactobacillus for use as health food for reducing (73) Proprietors: hypercholesterol level, comprises mixture of • Cambridge Enterprise Limited microbial cells belonging to Lactobacillus genus Cambridge having bile acid binding capacity and Cambridgeshire CB2 1TN (GB) cholestyramine" -& JP 2003 235501 A • Prokarium Limited (ANDERSEN INST BREAD & LIFE CO LTD; Keele Science Park TAKAKI BAKERY KK) 26 August 2003 Keele (2003-08-26) Staffordshire ST5 5SP (GB) • DATABASE WPI Section Ch, Week 200461 Thomson Scientific, London, GB; Class B04, AN (72) Inventors: 2004-630668 XP002587846 MIYAO M: • EDWARDS, Alexander "Formulation such as tablet and capsule Reading containing drug and foodstuff, comprises enteric RG6 6AD (GB) solublecoating on composition which comprises • SLATER, Nigel beneficial live microbial powder and bile Cambridge CB2 3RA (GB) adsorption components" -& JP 2004 250338 A (SUNSTAR CHEM IND CO LTD) 9 September 2004 (74) Representative: Sutcliffe, Nicholas Robert et al (2004-09-09) Mewburn Ellis LLP City Tower 40 Basinghall Street London EC2V 5DE (GB) (56) References cited: EP-A1- 1 281 752 EP-A1- 1 421 945 WO-A1-97/41741 WO-A1-2007/112747 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 384 190 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 384 190 B1 • FORD R P ET AL: "The effect of a rat plasma • EDWARDS ALEXANDER D; SLATER NIGEL K H: high-density lipoprotein subfraction on the "Formulation of a live bacterial vaccine for stable synthesis of bile salts by rat hepatocyte room temperature storage results in loss of acid, monolayers" FEBS LETTERS, ELSEVIER, bile and bile salt resistance" VACCINE, vol. 26, AMSTERDAM, NL LNKD- no. 45, 23 October 2008 (2008-10-23), pages DOI:10.1016/0014-5793(85)80215-5, vol. 179, no. 5675-5678, XP002587847 cited in the application 1, 1 January 1985 (1985-01-01), pages 177-180, XP025597771 ISSN: 0014-5793 [retrieved on 1985-01-01] • EDWARDS A D ET AL: "Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins"VACCINE, ELSEVIER LTD, GB, vol.27, no. 29, 12 June 2009 (2009-06-12) , pages 3897-3903, XP026802345 ISSN: 0264-410X [retrieved on 2009-04-23] cited in the application 2 1 EP 2 384 190 B1 2 Description ing buffer is currently the standard mode of delivery in ongoing human clinical trials of vaccine strains for dis- [0001] This invention relates to formulations for the oral eases such as Cholera [9] and Enterotoxic E. coli [10]. delivery of viable bacterial vaccine cells. [0008] The stomach has the ability to secrete hydro- [0002] Oral live bacteria delivery is currently used in 5 chloric acid and reduce the contents below pH 1. Few two main types of therapeutic application. Firstly, un- bacteria can survive to this pH [11] and dried live bacteria modified enteric bacteria strains identified from gut iso- have been shown to be even more sensitive than bacteria lates are of therapeutic interest in re-colonisation of the from fresh cultures [12]. An ’enteric’ coating may be used intestine after antibiotic treatment [1], in symptomatic re- to avoid the death of the live bacterial formulations in lief for sufferers of inflammatory intestinal disease [2], 10 gastric acid. An enteric coating is a polymer layer that and also in genetically engineered forms for delivery of will not dissolve in acidic conditions, but will dissolve in biological therapies (e.g. IL-10 [3]). Secondly, live bac- the intestine after stomach emptying, releasing the dry teria are attractive candidate vaccines. Currently, a bacteria into the upper small intestine. As noted above, number of human clinical trials are in progress testing existing enteric capsules of a live bacterial vaccine are various strains of attenuated live bacteria for protection 15 relatively ineffective, in spite of their ability to protect bac- against diseases such as Cholera, enterotoxic E. coli and teria from stomach acid [8]. Typhoid fever ([4]). Live bacterial vaccines have the ad- [0009] The intestine contains a complex mixture of en- vantage over conventional vaccines that they are admin- zymes and other microbicidal agents. Bile is secreted istered orally, avoiding injections and needles. Geneti- into the duodenum from the gall bladder. Bile generally cally engineered live bacterial vaccines may also carry 20 comprises at least 50% bile acids, which act as deter- heterologous DNA or antigens from pathogens or tu- gents to dissolve and digest fatty food components. Bile mours to stimulate or prime immune responses against acids are also potent at killing bacteria. Bacterial strains pathogen or tumour cells. that typically reside in intestinal sites, such as Salmonella [0003] Bacteria for live delivery are generally dried for spp, have evolved resistance mechanisms to detergents stability reasons. The alternative to dry formulation for 25 such as bile salts, allowing them to survive and grow in live bacterial delivery is a ’wet’ format, e.g. a food product the intestine. such as yoghurt. Live bacteria have significant stability [0010] Bacteria generally lose their resistance to bile problems in liquid forms, even if refrigerated. acids after drying or freezing. Dried bacteria which are [0004] A number of microencapsulation systems have released into the intestine from an enteric formulation are been proposed for oral delivery of bacteria [5], but all30 sensitive to bile acids and do not survive in the intestinal suffer from the same issue of degradation of the bacteria environment [12]. during storage, and a requirement for costly refrigeration [0011] The use of formulations comprising a first im- to reduce degradation. munogen and one or more second immunogens to de- [0005] Various techniques for producing dried bacteria liver the first immunogen to particular locations within the are known in the art. Most commonly, conventional35 gastrointestinal tract has been reported [18]. freeze-drying is used. In addition, there has been recent [0012] The present invention relates to the finding that focus on the use of di-saccharides such as trehalose and the incorporation of small amounts of a bile binding agent sucrose, which stabilise biomolecules and make dried intoformulations of dried viable cellssignificantly increas- bacteria more stable at room temperature [6], [7]. Disac- es the survival of the cells in the intestinal tract. According charide-stabilised dry bacteria, for example, may be con- 40 to the invention, the bile binding agent is cholestyramine veniently stored at room temperature. and the dried viable cells are dried viable bacterial vac- [0006] Currently, dried live bacteria are administered cine cells. This applies to the rest of the specification, orally in two common formats: enteric capsules of freeze- whenever reference is made to the invention. These for- dried bacteria, and sachets of freeze-dried bacteria to be mulations may therefore be useful for the oral delivery of resuspended in a bicarbonate buffer. Often, very high 45 live bacterial vaccine cells to the intestine. A first aspect doses of bacteria are given, and multiple doses are need- of the invention provides a solid formulation comprising ed to give only modest effects. Interestingly, clinical data dried viable bacterial vaccine cells and a bile binding indicates that the enteric capsule formulation is signifi- agent which is cholestyramine for use in a method of cantly less effective than the bicarbonate buffer system immunotherapy, as set out in claim 1. A second aspect [8][15], although little is known about why the enteric cap- 50 of the invention provides a method of producing the solid sules are relatively ineffective. formulation for use according to claim 1, said method [0007] Little is known about the mechanism of action comprising the steps according to claim 12. of the bicarbonate buffer system. The quantity of bicar- [0013] The bile binding agent allows aqueous liquids bonate buffer swallowed is not likely to absorb the acid to permeate the formulation but absorbs bile acids and secreted into the stomach, and so it seems likely that 55 retards their permeation through the formulation. This bacteria administered in this way will encounter some protects the dried viable cells from bile acid toxicity until acidity.
Recommended publications
  • Evaluation of Single Dose Sodium Polystyrene
    Open Access Original Article Sodium Polystyrene Sulfonate For Management of Hyperkalemia Pak Armed Forces Med J 2019; 69 (1): 37-42 EVALUATION OF SINGLE DOSE SODIUM POLYSTYRENE SULFONATE FOR MANAGEMENT OF HYPERKALEMIA AND ITS EFFECT ON OTHER SERUM ELECTROLYTES Shoaib Alam, Azfar Athar Ishaqui, Masood Ahmed Khan, Adnan Iqbal, Syed Hameez Jawed, Farah Khalid, Mir Muhammad Uzairullah, Muhammad Talha*, Usman Ashfaq*, Najam Zehra* University of Karachi, Karachi Pakistan, *Hamdard University Karachi Pakistan ABSTRACT Objective: To assess the effectiveness of sodium polystyrene sulphonate in treating hyperkalemia and its effect on different serum electrolytes level. Study Design: Quasi-experimental study. Place and Duration of Study: Lyari general hospital, 500 bedded tertiary care public sector hospital at Karachi, from Jan 2017 to Mar 2017. Material and Methods: Hyperkalemic patients were included in study who fulfilled inclusion criteria and were administered with single STAT 30 grams dose of Sodium Polystyrene Sulfonate. Serum electrolytes such as sodium, chloride, magnesium, phosphate and calcium were measured before and after 2 hours of administration of Sodium Polystyrene Sulfonate. Paired t-test was used as tool for statistical analysis. Results: Significant (p<0.05) decrease in serum potassium level with mean decrease of 0.61 mmol/L was observed in hyperkalemic patients (n=83) after single dose of Sodium Polystyrene Sulfonate. Among 83 studied patient, 67 (81%) recovered from hyperkalemia. Besides, there was significant (p<0.05) increase in sodium level with a mean increase of 2.26 mmol/L. Serum magnesium and calcium levels were significantly decreased (p<0.05) with mean difference of 0.02mmol/L and 0.13mmol/L respectively.
    [Show full text]
  • SODIUM POLYSTYRENE SULFONATE, USP Cation-Exchange Resin
    Kayexalate® SODIUM POLYSTYRENE SULFONATE, USP Cation-Exchange Resin DESCRIPTION Kayexalate, brand of sodium polystyrene sulfonate is a benzene, diethenyl-polymer, with ethenylbenzene, sulfonated, sodium salt and has the following structural formula: The drug is a cream to light brown finely ground, powdered form of sodium polystyrene sulfonate, a cation-exchange resin prepared in the sodium phase with an in vitro exchange capacity of approximately 3.1 mEq (in vivo approximately 1 mEq) of potassium per gram. The sodium content is approximately 100 mg (4.1 mEq) per gram of the drug. It can be administered orally or in an enema. CLINICAL PHARMACOLOGY As the resin passes along the intestine or is retained in the colon after administration by enema, the sodium ions are partially released and are replaced by potassium ions. For the most part, this action occurs in the large intestine, which excretes potassium ions to a greater degree than does the small intestine. The efficiency of this process is limited and unpredictably variable. It commonly approximates the order of 33 percent but the range is so large that definitive indices of electrolyte balance must be clearly monitored. Metabolic data are unavailable. INDICATION AND USAGE Kayexalate is indicated for the treatment of hyperkalemia. CONTRAINDICATIONS Kayexalate is contraindicated in the following conditions: patients with hypokalemia, patients with a history of hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, neonates with reduced gut motility (postoperatively or drug induced) and oral administration in neonates (see PRECAUTIONS). WARNINGS Intestinal Necrosis: Cases of intestinal necrosis, which may be fatal, and other serious gastrointestinal adverse events (bleeding, ischemic colitis, perforation) have been reported in association with Kayexalate use.
    [Show full text]
  • Dorset Medicines Advisory Group
    Dorset Medicines Advisory Group SHARED CARE GUIDELINE FOR THE USE OF PHOSPHATE BINDERS IN THE MANAGEMENT OF HYPERPHOSPHATAEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE. INDICATION This document provides guidance for the prescribing of phosphate binders for the management of hyperphosphatemia in patients receiving haemodialysis or peritoneal dialysis and patients with chronic kidney disease stage 4 or 5 who are not receiving dialysis. This shared care guideline covers adult patients under the care of the Dorset Renal Unit. Patients with chronic renal failure have reduced ability to excrete phosphate. Phosphate accumulation enhances parathyroid activity and leads to the calcification of arteries, significantly contributing to the excess cardiovascular morbidity in these patients, especially in younger age groups. Adequate control of serum phosphate levels is thought to be beneficial for the prevention of vascular and cardiac calcification in patients with renal failure and control of parathyroid hormone. A number of oral phosphate binders are available which may be used in the context of a multiple therapeutic approach. These include calcium acetate, calcium carbonate, calcium acetate/magnesium carbonate, lanthanum, sevelamer and sucroferric oxyhydroxide. These products may be used in combination with 1-hydroxycholecalciferol (alfacalcidol) or one of its analogues and/or cinacalcet to control the development of secondary hyperparathyroidism and renal bone disease. A calcium-based phosphate binder is generally used as the initial phosphate binder therapy for the treatment for hyperphosphatemia. Calcium acetate is preferred over calcium carbonate due to its lower elemental calcium content for the equivalent phosphate binding capacity, however patient preference in formulation should be taken into consideration. A non-calcium-based phosphate binder should be used in patients who cannot tolerate a calcium-based phosphate binder, whose serum calcium exceeds 2.5mmol/L or whose parathyroid levels are less than 15pmol/L.
    [Show full text]
  • AMBERLITE™ IRP69 Ion Exchange Resin Pharmaceutical Grade Cation Exchange Resin (Sodium Polystyrene Sulfonate USP)
    Product Data Sheet AMBERLITE™ IRP69 Ion Exchange Resin Pharmaceutical Grade Cation Exchange Resin (Sodium Polystyrene Sulfonate USP) Description AMBERLITE™ IRP69[1] resin is an insoluble, strongly acidic, sodium form cation exchange resin supplied as a dry, fine powder. AMBERLITE™ IRP69 Resin is suitable for use in pharmaceutical applications, both as an active ingredient and as a carrier for basic (cationic) drugs. It can be used for sustained release applications with compatible coating technologies. [1] The use of AMBERLITE™ pharmaceutical grade ion exchange resins as components of drug formulations is subject to the Food, Drug, and Cosmetic Act as amended. Regulatory Status A Drug Master File for AMBERLITE™ IRP69 is maintained with the United States Food and Drug Administration. Letters of authorization granting access to the file by FDA in support of NDA and ANDA submittals will be provided upon request. Similar help can also be offered in support of the registration of formulations containing AMBERLITE™ IRP69 in many other countries world- wide. AMBERLITE™ IRP69 is manufactured in accordance with Good Manufacturing Practices (cGMP) for bulk pharmaceutical chemicals Typical Properties AMBERLITE™ IRP69 complies with the compendial specifications for Sodium Polystyrene Sulfonate USP when tested in conformance to the compendial test methods presented in current USP/NF. Physical Properties Copolymer Styrene-divinylbenzene Type Strong acid cation Functional Group Sulfonic acid Physical Form Fine powder Chemical Properties Ionic Form as Shipped Na+ Heavy metals content [1] ≤ 10 ppm Potassium exchange capacity [1] 110–135 mg/g Water content [1] 10.0% maximum Ammonia salts [1] Negative to litmus paper Sodium content [1] 9.4%–11.5% Styrene content [1] 1 ppm maximum Particle Size § > 0.150 mm 1.0% maximum > 0.075 mm 10.0–25.0% §[1] Appears in current USP/NF Page 1 of 6 Form No.
    [Show full text]
  • The Indirect Implication of SARS-Cov-2 Resulting in Kayexalate Toxicity in a Patient with Acute Kidney Injury
    CODON P U B L I C A T I O N S Journal of Renal and Hepatic Disorders CASE REPORT: NEPHROLOGY The Indirect Implication of SARS-CoV-2 Resulting in Kayexalate Toxicity in a Patient with Acute Kidney Injury Charles E Middleton, IV, MD, William Daley, MD, Neha Varshney, MD Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA Abstract The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury (AKI), multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this dis- ease can itself lead to morbidity and mortality. We present a case that emphasizes the life-threatening gastrointestinal complications associated with the treatment of AKI in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death. Keywords: acute kidney injury; colonic perforation; COVID-19; Kayexalate; resins; sevelamer Received: 25 November 2020; Accepted after revision: 5 February 2021; Published: 27 February 2021. Author for correspondence: Neha Varshney, MD, Assistant Professor, Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4500, USA. Email: [email protected] How to cite: Middleton CE, et al.
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • Case Report Sevelamer Carbonate Crystal-Induced Colitis
    Hindawi Case Reports in Gastrointestinal Medicine Volume 2020, Article ID 4646732, 4 pages https://doi.org/10.1155/2020/4646732 Case Report Sevelamer Carbonate Crystal-Induced Colitis T. Lai ,1 A. Frugoli ,2 B. Barrows,3 and M. Salehpour4 1Community Memorial Health System, Graduate Medical Education, Ventura, CA, USA 2Community Memorial Health System, Graduate Medical Education, Department of Internal Medicine, Pacific Inpatient Physicians, Ventura, CA, USA 3Community Memorial Hospital, Department of Pathology, Ventura, CA, USA 4Community Memorial Hospital, Department of General Surgery, Ventura, CA, USA Correspondence should be addressed to T. Lai; [email protected] Received 19 February 2020; Accepted 30 March 2020; Published 24 July 2020 Academic Editor: Olga I. Giouleme Copyright © 2020 T. Lai et al. )is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hyperphosphatemia is a common and well-described complication of end-stage renal disease. Despite strict dietary constraints and compliance, phosphate binders such as calcium acetate and/or sevelamer carbonate are also needed to treat secondary hyperparathyroidism. )is case vignette describes an underrecognized adverse effect of a phosphate binder, sevelamer carbonate, inducing colitis in a 47-year-old male with insulin-dependent diabetes complicated by end-stage renal disease. He presented for recurrent abdominal pain with associated nausea and was found to have multiple circumferential lesions on computed to- mography including distal ascending, transverse, and proximal descending colon. Colonoscopy demonstrated nearly obstructing lesions worrisome for colonic ischemia or inflammatory bowel disease. Pathological review of histology demonstrated ragged colonic mucosa with ulcerative debris and nonpolarizing crystalline material at the sites of ulceration, morphologically consistent with the phosphate binder, sevelamer carbonate.
    [Show full text]
  • Kayexalate® (Sodium Polystyrene Sulfonate)
    Kayexalate® (sodium polystyrene sulfonate) – Drug Safety Communication • On October 22, 2015, the FDA announced that it is requiring the manufacturer of Kayexalate (sodium polystyrene sulfonate) to conduct studies to investigate Kayexalate’s potential to bind to other oral medications. • Kayexalate is indicated for the treatment of hyperkalemia. — Sodium polystyrene sulfonate is also generically available. Kionex® and SPS® are branded generics. • This safety communication was prompted by the FDA’s review of another potassium-lowering drug, Veltassa (patiromer). The FDA discovered that Veltassa bound to about half of the medications tested, some of which are commonly used in patients who require potassium-lowering drugs. — Similar to Veltassa, Kayexalate may also bind to other oral medications, which could decrease the effects of these medications. — Currently, the approved label for Kayexalate describes its potential to decrease absorption of lithium and thyroxine; however, extensive drug-drug interaction studies with Kayexalate have not been performed. • Patients should not stop taking their potassium-lowering drugs without talking to their healthcare provider. However, to reduce the risk of binding, prescribers and patients should consider separating the dose of Kayexalate from other oral medications by at least 6 hours. This includes both prescription and over-the-counter medications. • Healthcare providers should monitor blood levels or clinical response to other medications when appropriate. • If the studies conducted by the Kayexalate manufacturer, Concordia Pharmaceuticals, confirm significant interactions with other medications, the FDA will require all manufacturers of sodium polystyrene sulfonate products to update the drug labels to include information about these drug interactions. optumrx.com OptumRx specializes in the delivery, clinical management and affordability of prescription medications and consumer health products.
    [Show full text]
  • Dextromethorphan Polistirex Suspension, Extended
    ROBITUSSIN 12 HOUR COUGH RELIEF- dextromethorphan polistirex suspension, extended release GlaxoSmithKline Consumer Healthcare Holdings (US) LLC ---------- Drug Facts Active ingredient (in each 5 mL) Dextromethorphan polistirex equivalent to 30 mg dextromethorphan hydrobromide, USP Purpose Cough suppressant Uses temporarily relieves • cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants • the impulse to cough to help you get to sleep Warnings Do not use if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Allergy Alert Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions. Ask a doctor before use if you have • chronic cough that lasts as occurs with smoking, asthma, or emphysema • cough that occurs with too much phlegm (mucus) Stop use and ask a doctor if • side effects occur. You may report side effects to FDA at 1-800-FDA-1088. • cough lasts more than 7 days, cough comes back, or occurs with fever, rash, or headache that lasts. These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away 1-800-222-1222. Directions • shake bottle well before use • measure only with dosing cup provided.
    [Show full text]
  • Pharmaceutical Ion Exchange Resins – a Review
    Vol 4 | Issue 2 | 2014 | 134-145. e-ISSN 2249 – 7706 print-ISSN 2249– 7714 International Journal of Advanced Pharmaceutics www.ijapjournal.com PHARMACEUTICAL ION EXCHANGE RESINS – A REVIEW Ajay Bilandi1* and Amiya Kanta Mishra2 1*Research Scholar at Bhagwant University, Ajmer, Rajasthan, India. 2 Principal, College of Pharmaceutical Sciences, Puri, Orissa, India. ABSTRACT Ion exchange resins are water insoluble cross-linked polymers containing a salt-forming group at repeating positions on the polymer chain and have the ability to exchange counter-ions within aqueous solutions surrounding them. About 90 % of all ion exchange resins are based on a polystyrenic matrix. Synthetic ion exchange resins are usually cast as porous beads with considerable external and pore surface where ions can attach. Strong acid resins are so named because their chemical behaviour is similar to that of a strong acid. These resins are highly ionized in both the acid (R-SO3H) and salt (RSO3Na) form of the sulfonic acid group (-SO3H). Ion exchange is a process in which mobile ions from an external solution are exchanged for ions that are electrostatically bound to the functional groups contained within a solid matrix. There are various pharmaceutical grade resins like AMBERLITE® IRP88 , DUOLITE™ AP143/1083, INDION 204 , INDION 264 , TULSION® 335 TULSION® 345 , Kyron T etc. used as tablet disintegrant, active ingredients, as carrier for basic (cationic) drugs, application with compatible coating technique, mask objectionable taste associated with certain basic drugs, potassium reduction in blood, cholesterol reduction in blood, reduction of bile acid, treatment of hyperkalaemia and Stabilization of vitamin B12. This review covers the IER structure, chemistry, kinetics, ion exchange process, , loading of drug on resin, pharmaceutical grade resins ,drug delivery applications etc.
    [Show full text]
  • KAYEXALATE (Sodium Polystyrene Sulfonate) Is a Cream Or Light Brown Fine Powder of Sodium Polystyrene Sulfonate
    PRESCRIBING INFORMATION ® PrKAYEXALATE (Sodium Polystyrene Sulfonate) Cation - Exchange Resin sanofi-aventis Canada Inc. Date of Revision: 2905 Place Louis R.-Renaud September 19, 2018 Laval, Quebec H7V 0A3 Submission Control No.: 217331 s-a Version 5.0 dated September 19, 2018 KAYEXALATE Prescribing Information Page 1 of 12 DESCRIPTION KAYEXALATE (sodium polystyrene sulfonate) is a cream or light brown fine powder of sodium polystyrene sulfonate. KAYEXALATE is a cation-exchange resin prepared in the sodium phase, with an in vivo exchange capacity of approximately 1 mmol (in vitro approximately 3.1 mmol) of potassium per gram. The sodium content is approximately 4.1 mmol (100 mg) per gram of the drug. KAYEXALATE can be administered either orally or as an enema. ACTION Sodium polystyrene sulfonate is not absorbed from the gastrointestinal tract. As the resin passes through the gastrointestinal tract, the resin removes the potassium ions by exchanging it for sodium ions. Most of this action occurs in the large intestine, which excretes potassium ions to a greater degree than does the small intestine. Potassium exchange also occurs in the colon following retention of the resin, when administered as an enema. The efficiency of this process is limited and unpredictable. It commonly approximates the order of 33 per cent but the range is so large that definite indices of electrolyte balance must be clearly monitored. Metabolic data are unavailable. INDICATION KAYEXALATE is indicated for the treatment of hyperkalemia. CONTRAINDICATIONS KAYEXALATE should not be administered to patients with the following conditions: • serum potassium <5 mmol/L • history of hypersensitivity to polystyrene sulfonate resins • obstructive bowel disease KAYEXALATE should not be administered orally to neonates or in neonates with reduced gut motility (postoperatively or drug induced).
    [Show full text]
  • Reference ID: 4131527
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ----------------------- WARNINGS AND PRECAUTIONS ----------------------­ KAYEXALATE safely and effectively. See full prescribing information • Intestinal Necrosis: cases of intestinal necrosis and other serious for KAYEXALATE gastrointestinal events have been reported (5.1). • Electrolyte Disturbances: Severe hypokalemia can occur. (5.2). KAYEXALATE (sodium polystyrene sulfonate) powder for suspension, • Fluid overload in patient sensitive to high sodium intake: Monitor patients for oral or rectal use who are sensitive to sodium intake for signs of fluid overload. (5.3). Initial U.S. Approval: 1958 • Risk of aspiration: Acute bronchitis or bronchopneumonia caused by inhalation of sodium polystyrene sulfonate particles has been reported. --------------------------- INDICATIONS AND USAGE ---------------------------­ (5.4). KAYEXALATE is a potassium binder indicated for the treatment of hyperkalemia (1). ------------------------------ ADVERSE REACTIONS -----------------------------­ Limitation of Use: Adverse reactions reported include: anorexia, constipation, diarrhea, fecal KAYEXALATE should not be used an emergency treatment for life impaction, gastrointestinal concretions (bezoars), ischemic colitis, nausea, threatening hyperkalemia because of its delayed onset of action (1). vomiting (6). ----------------------- DOSAGE AND ADMINISTRATION ----------------------­ To report SUSPECTED ADVERSE REACTIONS, contact Concordia Oral: The average
    [Show full text]