Extemporaneous Ophthalmic Preparations Eman Ali Saeed Alghamdi Abdulmalik Yahya Al Qahtani Mazen M Sinjab Khalid Mohammed Alyahya 123 Extemporaneous Ophthalmic Preparations Eman Ali Saeed Alghamdi Abdulmalik Yahya Al Qahtani Mazen M. Sinjab Khalid Mohammed Alyahya Extemporaneous Ophthalmic Preparations Eman Ali Saeed Alghamdi Senior Drug Safety Specialist Pharmacovigilance Department Saudi Food and Drug Authority Riyadh Saudi Arabia Mazen M. Sinjab Senior Consultant Ophthalmic Surgeon Dr Mazen Sinjab Eye Clinic Medcare Hospital Dubai United Arab Emirates Abdulmalik Yahya Al Qahtani Consultant of Cornea, Cataract and Refractive Surgery, Ophthalmology Department Prince Sultan Military Medical City Riyadh Saudi Arabia Khalid Mohammed Alyahya Consultant Clinical Pharmacist Prince Sultan Military Medical City (PSMMC) Riyadh Saudi Arabia ISBN 978-3-030-27491-7 ISBN 978-3-030-27492-4 (eBook) https://doi.org/10.1007/978-3-030-27492-4 © Springer Nature Switzerland AG 2020 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland To my dear Father “Ali” (May God save him) Who taught me the meaning of life I will mention my name with his name all my life To my dear Mother “Mona” (May God save her) The source of love and the one whose prayers are behind my success I owe you who I am today To my dear Husband “Firas” (May God save him) Who has been a constant source of support and encouragement during the critical times Eman Ali Saeed Alghamdi Preface Pharmaceutical industries have greatly expanded their share of ophthalmic drugs in recent years However, physicians and pharmacists are frequently called to prepare sterile products intended for ophthalmic use due to a lack of availability of licensed drugs in the market The goal of this handbook is to produce a list of concise extemporaneous ophthalmic preparations and to standardize the formulation of the products by suggesting specific strength, route of administration, appropriate vehicle, and method of preparation This handbook contains the most appropriate formulation of each medication based on published and documented stability data It is divided into five sections The first part is an introduction to the principles of extemporaneous ophthalmic preparations in terms of ocular pharmacokinetics (Chap 1), factors affecting bioavailability and efficacy of topical eye preparations (Chap 2), ideal characteristics of ophthalmic drug delivery system (Chap 3), inactive ingredients used in the preparation of ophthalmic products (Chap 4), and the preservatives used in ophthalmic preparations (Chap 5) The second part is devoted to extemporaneous topical ophthalmic formulations It presents the topical ophthalmic drug forms (Chap 6), the extemporaneous compounding of ophthalmic products (Chap 7), and guidelines of the American Society of Health-System Pharmacists (ASHP) on pharmacy- prepared ophthalmic products (Chap 8) In this part, 24 preparations are discussed in terms of formulation, use and indications, the procedure of preparation, packaging and storage, and special precautions The third part presents the extemporaneous intraocular injections It is divided into intravitreal injections (Chap 10) and intracameral injections (Chap 11) Fifteen formulations are discussed in Chap 12 in terms of use and indications, the procedure of preparation, packaging and storage, and special precautions The fourth part discusses the extemporaneous subconjunctival injections Equipment and steps for subconjunctival injections are explained in Chap 13 Four formulations of the extemporaneous subconjunctival injections are presented in Chap 14 Finally, the fifth part is devoted to extemporaneous ophthalmic preparations in ocular oncology Five formulations are discussed in Chap 15 vii viii Preface The editors feel this book will make a welcome companion for many physicians and pharmacy practitioners who are frequently engaged in the compounding of sterile ophthalmic preparations Riyadh, Saudi Arabia Eman Ali Saeed Alghamdi Riyadh, Saudi Arabia Abdulmalik Yahya Al Qahtani Dubai, United Arab Emirates Mazen M. Sinjab Riyadh, Saudi Arabia Khalid Mohammed Alyahya Abstract In the daily practice of ophthalmologists, many diseases require special treatments for several reasons The disease might be rare enough, so no commercially prepared ophthalmic drugs are available Specific concentrations of medications are needed at eye tissue level to achieve the desired effect The medications should be directly delivered to the site of pathology In addition, there is a shortage of ready-made medications All the above reasons necessitate unlicensed extemporaneous ophthalmic formulation Mostly, these preparations are off-label products, which means an unapproved route of administration, unapproved indication, or unapproved age group Pharmacist, based on physicians’ requests under specific regulations and guidelines, prepares these formulations extemporaneously Moreover, these preparations are preservative-free; therefore, they have a short expiry date and require special precautions in preparations and storage This book is to cover this important topic It provides guidelines, concentrations, method of preparations, and storage conditions for pharmacists and provides indications and method of applications for ophthalmologists This book is the first of its kind in the market It covers all the unlicensed, off- label ophthalmic medications that ophthalmologists may need It gathers all the scattered updated information from different sources It delivers the information in a systemic, direct-to-the-point, and easy-to-find method ix Acknowledgment Firstly, I would like to acknowledge Professor Mazen M Sinjab for his academic guidance and great efforts to produce the book in this systematic and academic design We benefited to a great extent from his long experience in writing academic books in ophthalmology A special gratitude I give to Dr Abdulmalik Alqahtani for his contribution, advice, ideas, support, and patience in guiding me through this project Thank you for your enthusiasm to complete this work; your wealth of knowledge in the field of ophthalmology medications, in particular, is inspiring Thank you for giving me the opportunity to grow in this field of ophthalmic extemporaneous preparation I extend my sincere gratitude to Dr Khalid Alyahya whose contribution, support and encouragement helped me significantly to complete this book I would also like to acknowledge the support of other Prince Sultan Military Medical City colleagues along the way including the pharmacists and ophthalmologists who assisted us in preparing such guidance for sterile ophthalmic extemporaneous preparation Riyadh, Saudi Arabia Eman Ali Saeed Alghamdi xi Contents Part I Introduction to Extemporaneous Ophthalmic Preparations 1 Ocular Pharmacokinetics������������������������������������������������������������������������ 3 References�������������������������������������������������������������������������������������������������� 4 2 Factors Affecting Bioavailability and Efficacy of Topical Ophthalmic Preparations������������������������������������������������������ 5 References�������������������������������������������������������������������������������������������������� 6 3 Ideal Characteristics of Ophthalmic Drug Delivery System���������������� 9 References�������������������������������������������������������������������������������������������������� 9 4 Inactive Ingredients Used in the Preparation of Ophthalmic Products 11 References�������������������������������������������������������������������������������������������������� 11 5 Preservatives Used in Ophthalmic Preparations���������������������������������� 13 Reference �������������������������������������������������������������������������������������������������� 13 Part II Extemporaneous Topical Ophthalmic Formulations 6 Topical Ophthalmic Drug Forms������������������������������������������������������������ 17 References�������������������������������������������������������������������������������������������������� 18 7 Extemporaneous Compounding of Ophthalmic Products ������������������ 19 Reference �������������������������������������������������������������������������������������������������� 19 8 Guidelines of The American Society of Health-System Pharmacists (ASHP) on Pharmacy-Prepared Ophthalmic Products������������������������ 21 Reference �������������������������������������������������������������������������������������������������� 23 9 Formulations of Extemporaneous Topical Ophthalmic Preparations������ 25 9.1 Acetylcysteine Ophthalmic Solution������������������������������������������������ 25 9.2 Amikacin Ophthalmic Solution�������������������������������������������������������� 28 9.3 Amphotericin B Ophthalmic Solution���������������������������������������������� 28 9.4 Atropine Ophthalmic Solution���������������������������������������������������������� 30 xiii 14.4 Gentamicin Subconjunctival Injection 97 • Label each syringe and place it in an amber bag Expiration Date: 14 days Storage Conditions: Refrigerator Packaging: Sterile Luer-Lock® tuberculin syringe with sterile tamper-evident cap Special Instructions: For Subconjunctival only Keep in the refrigerator 14.3 Dexamethasone Phosphate Subconjunctival Injection [1, 2] • Description: Dexamethasone is a corticosteroid with main glucocorticoid activity It is available in a wide range of concentrations and dosage forms The Reported ophthalmic route of administration is intravitreal and subconjunctival injections in the treatment of some ocular inflammatory conditions • Use: Off Label Ocular inflammatory conditions • Preparation: –– Dexamethasone phosphate 1mg/0.25 ml (0.45 ml) Ingredients Quantity Dexamethasone mg/1 ml 0.45 ml Procedure: • From the Dexamethasone phosphate vial, withdraw 0.45 ml (1 mg/0.25 ml dose plus 0.2 ml overfill) into a syringe through a 5-μm filter needle • Replace the filter needle with a fresh regular needle • Transfer the solution to a 2-ml sterile empty vial Expiration Date: 24 h Storage Conditions: Refrigerator Packaging: Sterile Luer-Lock® tuberculin syringe with sterile tamper-evident cap Special Instructions: Keep out of reach of children Keep in the refrigerator For subconjunctival use only 14.4 Gentamicin Subconjunctival Injection [1, 6, 7] • Description: Gentamicin is an aminoglycoside antibiotic obtained from cultures of Micromonospora purpura It is available as a mixture of the sulfate salts of Gentamicin C1, C2, and C1A. Mechanism of action is by inhibiting microbial 98 14 Formulations of Extemporaneous Subconjunctival Injections protein synthesis in susceptible pathogens Gentamicin is physically incompatible with semisynthetic Penicillin such as Ampicillin For this reason, they should never be mixed in the same syringe or bottle for ophthalmic use It is recommended that concomitant use is separated by 15 min Subconjunctival injection of gentamicin would be a poor choice due to its toxicity It may lead to pain, hyperemia, and conjunctival edema, while severe retinal ischemia has followed intraocular injections • Use: Off Label Treatment of bacterial eye infection and corneal ulceration due to susceptible organisms • Preparation: –– Gentamicin 20 mg/0.5 ml (0.5 ml) Ingredients Gentamicin 80 mg/2 ml Quantity 0.5 ml Procedure: • Under a laminar airflow workbench, aseptically withdraw 0.7 ml (50 mg/0.5 ml plus 0.2ml overfill) from the Gentamicin vial into a syringe through a 0.22-μm filter needle • Replace the filter needle with a fresh regular needle • Transfer the solution to a sterile 2 ml vial • Seal and label the vial Expiration Date: 24 h Storage Conditions: Refrigerator Packaging: Sterile Luer-Lock® tuberculin syringe with sterile tamper-evident cap Special Instruction: Keep out of reach of children Keep in the refrigerator For subconjunctival use only References Reynolds LA, Closson RG. Extemporaneous ophthalmic preparations Am J Ophthalmol 1994;117(2):277 Trissel LA. Trissel’s stability of compounded formulations 4th ed Washington DC: American Pharmacists Association; 2009 p. 26–7 Doctor PP, Bhat PV, Foster CS. Subconjunctival bevacizumab for corneal neovascularization Cornea 2008;27(9):992–5 Genentech Avastin Summary of product characteristics (2010) Available at http://www ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000582/ WC500029271.pdf Accessed Jul 2012 References 99 Novartis Lucentis summary of product characteristics (2012) Available at https://www.medicines.org.uk/emc/history/19409/SPC/Lucentis+10+mg+ml+solution+for+injection Accessed Jul 2012 Jenkins CD, McDonnell PJ, Spalton DJ. Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery Br J Ophthalmol 1990;74(12):734–8 Trissel LA, Allwood MC, Haas DP, Hale KN, American Society of Hospital Pharmacists Handbook on injectable drugs, vol 14 Bethesda: American Society of Health-System Pharmacists; 2007 Part V Extemporaneous Ophthalmic Preparations in Ocular Oncology In the medical literature, there are few medications that are used as extemporaneous ophthalmic preparation in ocular oncology In this section, only evidence-based preparations will be mentioned Chapter 15 Extemporaneous Ophthalmic Preparations in Ocular Oncology 15.1 5-Fluorouracil Ophthalmic Solution [1–7] • Description: 5-Fluorouracil (5-FU) is a structural analog of thymine, which is a fluorinated pyrimidine antagonist The pharmacological effect comes from impairing of DNA and RNA synthesis in tumor cells and normal cells as well However, it is relatively more selective in cancerous cells due to higher DNA and RNA synthesis It is applied topically at a concentration of 1% • Use: Off Label Treatment of Ocular Surface Squamous Neoplasia (OSSN), including a broad spectrum of conjunctival malignancies, ranging from mild epithelial dysplasia to invasive squamous carcinoma 5-FU has shown an efficacy of 85–100%, with a tumor recurrence rate ranging from 1.1% to 43% • Dose: There are two methods to apply the drops depending on the study: –– One drop four times a day for 4 weeks –– One drop four times a day for week followed by a drug holiday of weeks • Preparation: • Caution: Hazardous medication Must be prepared in compliance with USP –– 5-Fluorouracil 10 mg/ml % in 5 ml Ingredients 5-Fluorouracil 50 mg/ml vial (10 ml) Sodium chloride 0.9%(preservative free) Quantity 50 mg 4 ml © Springer Nature Switzerland AG 2020 E A S Alghamdi et al., Extemporaneous Ophthalmic Preparations, https://doi.org/10.1007/978-3-030-27492-4_15 103 104 15 Extemporaneous Ophthalmic Preparations in Ocular Oncology Procedure: • Aseptically withdraw 1 ml of 5-FU (50 mg) into a syringe by a 0.22-μm filter needle • Replace the filter needle of the 5-FU-solution syringe by a fresh regular needle, and then transfer to a sterile ophthalmic dropper bottle • Add 4 ml of sodium chloride 0.9 % for injection (preservative free) • Cap dropper bottle and shake to mix before use • Label with chemotherapy handling and disposal precautions Expiration Date: days Storage Conditions: Refrigerator Packaging: Sterile dropper bottle (plastic or glass) Special Instructions: Cytotoxic precaution (special handling and disposal required) Keep out of reach of children For ophthalmic use only Keep in the refrigerator 15.2 Melphalan Intravitreal Injection [8–12] • Description: Melphalan is a cell cycle nonspecific chemotherapeutic agent It is capable of killing tumor cells in any phase of the cell cycle As a bischloroethylamine alkylating agent, melphalan forms covalent cross-links with DNA or DNA protein complexes, thereby, resulting in cytotoxic, mutagenic, and carcinogenic effects The result of the alkylation process is misreading of the DNA code and the inhibition of DNA, RNA, and protein synthesis in rapidly proliferating tumor cells Melphalan is approved for intravenous treatment for Hematopoietic stem cell transplant and Multiple myeloma Moreover, it is used in the form of an intravitreal injection to treat conditions of vitreous disease in retinoblastoma Intravitreal injection is prepared in a concentration of 0.2 mg/ml, and the injected dose is 20 mcg, which can be cumulatively increased by 2–4 mcg up to 30 mcg depending on the patient’s situation • Use: Off Label Treatment of vitreous disease in retinoblastoma • Preparation: –– Melphalan 20 mcg/0.1 ml (0.3 ml) Ingredients Melphalan hydrochloride powder The Supplied diluent Sodium chloride 0.9% (preservative free) Quantity 50 mg 10 ml QS: 25 ml 15.3 Methotrexate Intravitreal Injection 105 Procedure: • Under a laminar airflow workbench, aseptically reconstitute the 50 mg of Melphalan hydrochloride powder with the 10 ml of supplied diluent, and shake to mix This is a Melphalan Vial A of mg/ml concentration • Withdraw 1 ml from vial A and transfer to 30 ml sterile empty vial This is vial B • Add 24 ml of preservative-free 0.9% Sodium chloride to Vial B and shake to mix The concentration in vial B becomes 0.2 mg/ml • From Vial B, withdraw 0.3 ml (20 mcg/0.1 ml dose plus 0.2 ml overfill) into a syringe by a 5-μm filter needle, and then replace the filter needle with a fresh regular needle • Transfer the solution to a 2-ml sterile empty vial • Seal and label the vial Expiration Date: 3 h Storage Conditions: Refrigerator Packaging: Sterile Luer-Lock® tuberculin syringe with sterile tamper-evident cap Special Instruction: For intravitreal injection only Keep in the refrigerator Protect from light 15.3 Methotrexate Intravitreal Injection [13–16] • Description: Methotrexate is a chemotherapeutic agent that acts by inhibiting dihydrofolate reductase, the enzyme that reduces folic acid to tetrahydrofolic acid Tetrahydrofolates are utilized in the synthesis of nucleotides and thymidylate This inhibition interferes with DNA synthesis and repair, and cellular reproduction Generally, actively proliferating tissues are more sensitive to the effect of methotrexate Methotrexate is used intravitreally as the first-line treatment of ocular involvement in primary vitreoretinal lymphoma (PVRL) without central nervous system (CNS) involvement with sustainable morbidity Intravitreal methotrexate injections is prepared at a concentration of 0.4 mg/0.1 ml It is administered two times per week for weeks, once per week for weeks, and once monthly for the next months The most commonly reported complications are a transient elevation of intraocular pressure and corneal epitheliopathy that subsided by increasing the intervals between consecutive injections • Use: Off Lable CD20-positive PVRL without CNS involvement • Preparation: 106 15 Extemporaneous Ophthalmic Preparations in Ocular Oncology –– Methotrexate 0.4 mg/0.1 ml (0.3 ml) Ingredients Methotrexate “Ebewe”, Liba Lab A.S Water for injection(preservative free) Quantity 50 mg/2ml 10.5 ml Procedure: • Under a laminar airflow workbench, aseptically dilute 50 mg/2 ml of Methotrexate with 10.5 ml of preservative-free water for injection and shake to mix This is a methotrexate vial of mg/ml • Withdraw 0.3 ml (0.4 mg/0.1 ml dose plus overfill) from the Methotrexate vial mg/1 ml into a sterile Luer-Lock® tuberculin syringe • Cap the syringe with a tamper-resistant sterile cap • Label each syringe and place it in an amber bag Expiration Date: 24 h Storage Conditions: Refrigerator Packaging: Sterile Luer-Lock® tuberculin syringe with sterile tamper-evident cap Special Instruction: For intravitreal injection only Keep in the refrigerator Protect from light 15.4 Mitomycin-C Ophthalmic Solution [17–30] • Description: Mitomycin-C (MMC) is an antineoplastic antibiotic agent, produced by Streptomyces caespitosus It is a potent alkylating agent The treatment is usually limited by the side effect related to Mitomycin-C including photophobia, dry eye, punctal stenosis, persistent epithelial defects, Limbal Stem Cell Deficiency (LSCD), and allergic reactions, all of which are very common Mitomycin-C has been administered topically in two different concentrations of 0.02% and 0.04% based on the indication • Use: Off Label Treatment of Ocular Surface Squamous Neoplasia It is used as topical ophthalmic drops as a primary treatment or adjunctive to surgical resection either before the surgery as a chemoreduction measure, during the surgery (intraoperatively), or after the surgery as a chemopreventive measure to reduce the risk of recurrence • Dose: Treatment of Ocular Surface Squamous Neoplasia Based on one study, MMC 0.02% was used as one drop three times daily for at least two 1-week courses, 15.4 Mitomycin-C Ophthalmic Solution 107 and based on another study 0.04% was used as one drop four times daily for at least two 1-week courses In both studies, that was in both primary and adjunctive treatments • Preparation: • Caution: Hazardous medication Must be prepared in compliance with USP –– First Formulation: Mitomycin-C 0.02% (0.2 mg/ml) Ingredients Mitomycin injection mg/vial (Powder) Distilled water used for injection (preservative free) Quantity 0.2 mg/ml (0.02%) 5 mg 25 ml –– Second Formulation: Mitomycin-C 0.04% (0.4 mg/ml) Ingredients Mitomycin injection mg/vial (Powder) Distilled water for used injection(preservative free) Quantity0.4 mg/ml (0.04%) 5 mg 12.5 ml Procedure: • Under the vertical laminar airflow hood, a high-level disinfectant is sprayed on the outer walls of the filters which contain, respectively, the MMC vial and the distilled water used for injection (preservative-free) to prevent contamination of the laminar flow hood • Aseptically reconstitute (5 mg) of MMC vial with (25 ml) of distilled water to obtain a concentration of 0.2 mg/ml (0.02%), or (12.5 ml) of distilled water to obtain a concentration of 0.4 mg/ml (0.04%) • From the MMC solution vial, withdraw the whole contents into a syringe by a 0.22-μm filter needle and transfer the solution to the sterile ophthalmic dropper bottle • Cap the dropper bottle and label with chemotherapy handling and disposal precaution Expiration Date: 14 days Storage Conditions: Refrigerator Protect from light Packaging: Sterile amber dropper bottle (plastic or glass) Special Instructions: Cytotoxic precaution (special handling and disposal required) Keep out of reach of children For ophthalmic use only Keep in the refrigerator Protect from light 108 15 Extemporaneous Ophthalmic Preparations in Ocular Oncology 15.5 Rituximab Intravitreal Injection [31–35] • Description: Rituximab is a humanized monoclonal mouse anti-CD20 antibody that binds CD20 It is approved for intravenous treatment for B-cell non-Hodgkin's lymphoma, including diffuse large B-cell lymphoma that is refractory to other chemotherapy regimens However, it is used in the form of an intravitreal injection to treat conditions associated with CD20-positive PVRL without CNS involvement It is prepared in a concentration of mg/0.1 ml, in terms of one-course protocol, once weekly for four weeks Intravitreal Rituximab may be an alternative option to intravitreal methotrexate due to the lower level of toxicity • Use: Off Label CD20-positive PVRL without CNS involvement • Preparation: –– Rituximab mg/0.1 ml (0.3 ml) Ingredients Rituximab (Rituxan, Genentech, Inc., San Francisco, CA), 10 mg/1 ml Quantity 0.3 ml Procedure: • Under a laminar airflow workbench, aseptically withdraw 0.3 ml (1 mg/0.1 ml dose plus overfill) from the Rituximab vial 100 mg/10 ml • Withdraw a solution into a sterile Luer-Lock® tuberculin syringe, and cap with a tamper-resistant sterile cap • Label each syringe and place it in an amber bag Expiration Date: 24 h Storage Conditions: Refrigerator Packaging: Sterile Luer-Lock® tuberculin syringe with sterile tamper-evident cap Special Instruction: For intravitreal injection only Keep in the refrigerator Protect from light References Fuhrman LC, Godwin DA, Davis RA. Stability of 5-fluorouracil in an extemporaneously compounded ophthalmic solution Int J Pharm Compd 2000;4:320–3 Midena E, Angeli CD, Valenti M, de Belvis V, Boccato P. Treatment of conjunctival squamous cell carcinoma with topical 5-fluorouracil Br J Ophthalmol 2000;84(3):268–72 References 109 Gichuhi S, Macharia E, Kabiru J, et al Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial Lancet Glob Health 2016;4(6):e378–85 Parrozzani R, Lazzarini D, Alemany-Rubio E, Urban F, Midena E. Topical 1% 5-fluorouracil in ocular surface squamous neoplasia: a long-term safety study Br J Ophthalmol 2011;95(3):355–9 Joag MG, Sise A, Murillo JC, et al Topical 5-fluorouracil 1% as primary treatment for ocular surface squamous neoplasia Ophthalmology 2016;123(7):1442–8 Parrozzani R, Frizziero L, Trainiti S, et al Topical 1% 5-fluorouracil as a sole treatment of corneoconjunctival ocular surface squamous neoplasia: long-term study Br J Ophthalmol 2017;101(8):1094–9 Bahrami B, Greenwell T, Muecke JS. Long-term outcomes after adjunctive topical 5-flurouracil or mitomycin C for the treatment of surgically excised, localized ocular surface squamous neoplasia Clin Exp Ophthalmol 2014;42(4):317–22 Munier FL, Gaillard MC, Balmer A, Soliman S, Podilsky G, Moulin AP, Beck-Popovic M. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications Br J Ophthalmol 2012;96(8):1078–83 Product Information: ALKERAN(R) oral tablets, melphalan oral tablets Rockville, MD: ApoPharma USA Inc (per FDA); 2011 10 Gilman AG, Rall TW, Nies AS, et al Goodman and Gilman’s the pharmacological basis of therapeutics 8th ed Elmsford, NY: Pergamon Press; 1990 11 Braunwald E, Isselbacher KJ, Petersdorf RG, et al Harrison’s principles of internal medicine 12th ed New York, NY: McGraw-Hill Book Company; 1990 12 Betcher DL, Burnham N. Melphalan J Pediatr Oncol Nursing 1990;7:35–6 13 Chan CC. Primary intraocular lymphoma: clinical features, diagnosis, and treatment Clin Lymphoma 2003;4(1):22–9 14 Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB, et al Primary vitreoretinal lymphoma: a report from an international primary central nervous system lymphoma collaborative group symposium Oncologist 2011;16(11):1589–99 15 Chan CC, Sen HN. Current concepts in diagnosing and managing primary vitreoretinal (intraocular) lymphoma Discov Med 2013;15(81):93 16 Ozkan EB, Ozcan AA, Alparslan N. Intravitreal injection of methotrexate in an experimental rabbit model: determination of pharmacokinetics Ind J Ophthalmol 2011;59(3):197 17 Trissel L. Handbook on injectable drugs 7th ed; 1992 p. 625–6 18 McEvoy GK, editor AHFS drug information 93 Bethesda, MD: American Society of Health- System Pharmacists; 1992 p. 628–30 19 Singh P, Singh A. Mitomycin-C use in ophthalmology IOSR J Pharm 2013;3:12–4 20 Hirst LW. Randomized controlled trial of topical mitomycin C for ocular surface squamous neoplasia: early resolution Ophthalmology 2007;114(5):976–82 21 Chen C, Louis D, Dodd T, Muecke J. Mitomycin C as an adjunct in the treatment of localised ocular surface squamous neoplasia Br J Ophthalmol 2004;88(1):17–8 22 Rahimi F, Ali PF, Ghazizadeh HH, Saleh SB, Hashemian M, Mehrdad R Topical mitomycin-C for treatment of partially-excised ocular surface squamous neoplasia 2009;12(1):55–9 23 Gupta A, Muecke J. Treatment of ocular surface squamous neoplasia with Mitomycin C. Br J Ophthalmol 2010;94(5):555–8 24 Russell HC, Chadha V, Lockington D, Kemp EG. Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications Br J Ophthalmol 2010;94(10):1316–21 25 Birkholz ES, Goins KM, Sutphin JE, Kitzmann AS, Wagoner MD. Treatment of ocu lar surface squamous cell intraepithelial neoplasia with and without mitomycin C. Cornea 2011;30(1):37–41 26 Besley J, Pappalardo J, Lee GA, Hirst LW, Vincent SJ. Risk factors for ocular surface squamous neoplasia recurrence after treatment with topical mitomycin C and interferon alpha-2b Am J Ophthalmol 2014;157(2):287–93 110 15 Extemporaneous Ophthalmic Preparations in Ocular Oncology 27 Kalamkar C, Radke N, Mukherjee A, Radke S. Topical mitomycin-C chemotherapy in ocular surface squamous neoplasia J Clin Diagnos Res 2016;10(9):NJ01 28 Singh S, Mittal R, Rath S. Multifocal ocular surface squamous neoplasia Ophthal Plastic Reconst Surg 2017;33(6):e156–7 29 Wilson MW, Hungerford JL, George SM, Madreperla SA. Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia Am J Ophthalmol 1997;124(3):303–11 30 Frucht-Pery J, Sugar J, Baum J, Sutphin JE, Pe’er J, Savir H, et al Mitomycin C treatment for conjunctival—corneal intraepithelial neoplasia: a multicenter experience Ophthalmology 1997;104(12):2085–93 31 Scott SD. Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin’s lymphoma Cancer Pract 1998;6(3):195–7 32 Rubenstein JL, Treseler P, O'Brien JM. Pathology and genetics of primary central nervous system and intraocular lymphoma Hematol Oncol Clin 2005;19(4):705–17 33 Grimm SA, Pulido JS, Jahnke K, Schiff D, Hall AJ, Shenkier TN, et al Primary intraocular lymphoma: an international primary central nervous system lymphoma collaborative group report Ann Oncol 2007;18(11):1851–5 34 Hashida N, Ohguro N, Nishida K. Efficacy and complications of intravitreal rituximab injection for treating primary vitreoretinal lymphoma Transl Vision Sci Technol 2012;1(3):1–1 35 Hashida N, Nakai K, Saitoh N, Nishida K. Association between ocular findings and preventive therapy with onset of central nervous system involvement in patients with primary vitreoretinal lymphoma Graefes Arch Clin Exp Ophthalmol 2014;252(4):687–93 Index A Acetylcysteine, 25–27 Actinomyces, 33, 48, 82 α-hydroxyprogesterone, 46 α-methyl, 46 AmBisome®, 29, 70 Amikacin, 28, 69, 95, 96 Amino acids, 25, 39 Aminoglycoside, 28, 44, 50, 69, 97 Amphotericin B, 28–30, 70 Ampicillin, 44, 51 Amycolatopsis orientalis, 51 Anti-angiogenic, 45 Antibacterial, 33, 36, 37, 41, 73, 82 Antimicrobial, 32, 33, 35, 36, 44, 50, 74 Antineoplastic, 44, 47, 106 Anti-proliferative, 44–45 Artificial tears, 17, 25, 28, 34, 39, 51, 52 Aspergillus, 28, 29, 53, 70, 86 Atopic keratoconjunctivitis (AKC), 50 Atropine, 30–31 Autologous serum, 31–32 B Bacillaceae, 32 Bacillus, 32, 41 Bacitracin, 32–33 Bacterial, 28, 33, 34, 36–38, 41, 48, 51, 52, 69, 73, 86, 95, 98 Bactericidal, 33, 35, 36, 48, 51, 73–75, 82 Balanced salt solution (BSS), 50, 71, 81, 84 Band keratopathy, 42 Benzalkonium chloride (BAK), 11, 13, 26, 54 Beta-lactam, 48, 82 Beta-lactamase, 35, 37, 49, 51, 74 Bevacizumab, 72 Blepharitis, 34, 39 Buffers, 5, 28 C Calcineurin, 39, 49 Calcium, 42 Candida, 28, 29, 53, 70, 86 Carcinoma, 43 Castor oil, 39, 40 Cataract, 36, 75, 83 Cefazolin, 33–35, 73 Ceftazidime, 35–36 Ceftriaxone, 37–38 Cephalosporin, 33, 35–38, 73–75 Cidofovir, 76 Clindamycin, 38–39, 77 Clostridia, 33 CMV, see Cytomegalovirus (CMV) Colistimetate, 41 Colistin, 41 Collagenase, 42, 46 Condyloma acuminate, 45 Conjunctivitis, 34, 39, 45 Corticosteroid, 78 Corynebacterium, 33 Cryptococcus, 28, 70 Curvularia, 29, 70 Cyclic polypeptide, 39 Cyclodextrins, Cyclosporine, 39–40 Cytomegalovirus (CMV), 79, 80 Cytotoxic, 43, 45, 48, 79, 81 © Springer Nature Switzerland AG 2020 E A S Alghamdi et al., Extemporaneous Ophthalmic Preparations, https://doi.org/10.1007/978-3-030-27492-4 111 112 D D-Alanyl-D-alanine, 85 Deoxycholate, 28, 29, 70 Dexamethasone, 78 Disodium edetate, 42 Distilled water, 29, 30, 33–37, 41, 42, 45–49, 52, 71, 73, 77, 80, 82, 84 DNA, 43, 78 DNA polymerase, 76 Dysplasia, 43, 45 E Edetate disodium (EDTA), 42 Endophthalmitis, 36, 38, 75 Enzymolysis, Epitheliotrophic, 31 Ergosterol, 53, 86 F 5-Fluorouracil (5-FU), 43, 103 Fluconazole, 53 Foscarnet, 78, 79 Free D-Alanyl-D-alanine, 52 Fungal, 28, 29, 53 Fungi, 41, 52, 85 Fusarium, 28, 29, 53, 70, 86 G Ganciclovir, 79 Gentamicin, 28, 44, 50, 69, 97 Giant papillary conjunctivitis, 50 Glaucoma, 47, 72 Glioblastoma, 72, 96 Glucocorticoid, 78, 97 Glycopeptide, 51 Glycoprotein, 44 Gram-negative, 28, 35, 37, 41, 48, 52, 69, 74, 82, 85 Gram-positive, 33, 37, 41 Growth factors, 31 Guanine, 79 H Haemophilus influenza, 33 Hemolysis, 32 Hemorrhagic conjunctivitis, 45 Hepatitis, 45 H-index, 32 Hydrolyzed, 41 Hydrophilicity, Hyperaemia, 45 Index Hyperplasia, 45 Hypromellose, 26 I Immunobullous, 31 Immunoglobulin, 31 Immunomodulatory, 39 Inserts, 17, 93 Interferon, 44–45 Interleukin, 39 Intracameral, 3, 19, 67, 71, 75, 83, 86 Intravitreal, 3, 19, 63, 64, 70, 71, 76–79, 85, 104–106, 108 Iontophoresis, 18 K Kaposi, 45 Keratoconjunctivitis, 25, 26, 39 Keratopathy, 32 L L-cysteine, 25 Leukemia, 45 Licheniformis, 32 Lipophilic, 39 Lipophilicity, Liposomal, 29, 30 Liposomes, 17 Liquifilm tears, 39, 40 Lymphoid, 45 Lymphoma, 45, 105, 108 M Macrolide, 49 Magnesium, 49 Medroxyprogesterone, 46 Melanoma, 45 Melphalan, 104, 105 Metabolism, Methanesulfonate, 41 Methotrexate, 105, 106, 108 Methyl, 13 Micro-emulsions, Micromonospora Purpura, 44 Mitomycin-C (MMC), 47–48, 106, 107 Mucolytic, 25 Mucopeptide, 35, 36 Mucoproteins, 25 Multi-Drug Resistant Pseudomonas Aeruginosa (MDR-PA), 41 Index N Nanoparticles, 17 Neisseria, 33 Neoplasia, 43, 47, 103, 106 Niosomes, 18 Nocardia, 51 Nucleosides, 41, 79 O Olive oil, 39 P Paecilomyces, 53, 86 Penicillin, 38, 44, 48–49 Penicillinase, 48, 82 Penicillium Chrysogenum, 48 Permeability, 11 Pharmacokinetics, Phenylacetic, 48, 82 Plasmin, 83 Polyaminopropyl biguanide, 13 Polyethylene, 31 Polymerase, 78 Polymyxin, 41 Polyvinyl alcohol, 40 Potassium, 48–49, 82 Povidone, 39, 40 Povidone-iodine, 63, 64, 67, 93 Propylparaben, 13 Pseudomonas, 35 Purine, 76, 79 Pyrimidine, 43, 103 R Retinitis, 76, 79 Retinoblastoma, 104 Ringer, 86 RNA, 43, 78, 103, 104 S Sarcoma, 45 Scedosporium, 53, 86 Sjogren’s syndrome, 25, 31 Sodium chloride, 26, 29, 31, 32, 38, 43, 69, 75, 76, 81, 84, 85, 104, 105 113 Solubility, 5, 11, 21 Spirochetes, 48, 82 Stability, 5, 22, 37 Staphylococci, 33 Stem cell, 47, 104, 106 Sterility, 5, 21 Stevens-Johnson syndrome, 31 Streptococci, 33 Streptomyces, 47, 49, 50, 106 Sulfamethyl, 41 Sulfate, 28, 30, 44, 49, 51, 69, 95 Sulphydryl, 25 T Tacrolimus, 49–50 T-cells, 49, 50 Tertiary amine antimuscarinic alkaloid, 30 Tetrahydrofolates, 105 Tetrahydrofolic acid, 105 Thimerosal, 13 Thymidine, 78 Thymidylate, 105 Thymine, 43, 103 Tissue plasminogen activator (TPA), 83 Tobramycin, 28, 50–51, 69 Tonicity, 5, 11, 21 Toxic anterior segment syndrome (TASS), 68 Treponema pallidum, 33 Triazole, 53 U Uveitis, 63 V Vancomycin, 51–53, 85 Vascular endothelial growth factor (VEGF), 72, 96 Vernal keratoconjunctivitis (VKC), 50 Viral DNA, 79 Viscosity, 6, 11, 17, 34 Vitamins, 31 Voriconazole, 53–54, 86 Y Yeast, 52, 85 .. .Extemporaneous Ophthalmic Preparations Eman Ali Saeed Alghamdi Abdulmalik Yahya Al Qahtani Mazen M. Sinjab Khalid Mohammed Alyahya Extemporaneous Ophthalmic Preparations Eman Ali Saeed Alghamdi... Consultant Clinical Pharmacist Prince Sultan Military Medical City (PSMMC) Riyadh Saudi Arabia ISBN 97 8-3 -0 3 0-2 749 1-7 ISBN 97 8-3 -0 3 0-2 749 2-4 (eBook) https://doi.org/10.1007/97 8-3 -0 3 0-2 749 2-4 © Springer... compounding of sterile ophthalmic preparations Riyadh, Saudi Arabia Eman Ali Saeed Alghamdi Riyadh, Saudi Arabia Abdulmalik Yahya Al Qahtani Dubai, United Arab Emirates Mazen M. Sinjab Riyadh,