How Stable Are Medicines Moved From Original Packs Into Compliance Aids

For personal use only. Not to be reproduced without permission of the editor ([email protected]) Articles How stable are medicines moved from original packs into compliance aids? In this article, Claire Church and Jane Smith have compiled a table based on information received from manufacturers about the possible stability of their medicines after removal from their packaging and placement in compliance aids he use of compliance aids has increased in both primary and secondary care over recent years. Compliance aids aim to act as a reminder for patients to take their medicines, enabling them to manage their own often complex and confusing drug regimens. They also act as a visual prompt for carers, indicating that patients have taken their medicines, or at least removed them from the device. The use of these aids involves the transfer of medicines from the manufacturer’s original packaging to the compliance aid. The original packaging is designed to protect the contents to appropriate pharmacopoeial and quality standards for a variety of criteria, eg, water vapour transmission, as required in the product licence. However, the compliance aid cannot guarantee the same level of protection. Many systems are not disposable and are frequently reused without cleaning.The hazards associated with physical, chemical and microbiological cross-contamination could be a major risk factor. All other dispensing containers are designed for single use. Compliance aids have limited available space for each dose, are not airtight and offer less moisture and light protection than original packs. Doubts are raised as to the stability of medicines that have been transferred to compliance aids: is there a deterioration in quality and can this result in a reduction of efficacy to an unacceptable level? Despite the increased dispensing of medicines in this way, guidance on their stability in these systems is limited and little new information has been published in recent years. Certain products are particularly unsuitable for transferring into compliance aids, but even this information is often not readily available. The Royal Pharmaceutical Society, in it “Medicines, ethics and practice” guide (section 3.4.7) says that “medicines should not be left in sealed monitored dosage systems for T longer than eight weeks” and that “certain medications should not be placed in monitored dosage systems. These include effervescent tablets, dispersible tablets, buccal tablets, sublingual tablets, significantly hygroscopic preparations and solid dose cytotoxic preparations.” A general article by Roger Walker in The Pharmaceutical Journal in 19922 contained information on around 70 products from 53 pharmaceutical manufacturers. The leading article in the same journal discussed the lack of data and concluded: “Manufacturers and regulatory authorities urgently need to catch up with current practice.”3 In response to these articles a series of letters appeared a few weeks later.4 A medicines and prescribing bulletin for health care professionals in East Lancashire published data on approximately 30 products in November 2000.5 The medicines information department at Pinderfields General Hospital has collated data that are largely derived from pharmaceutical manufacturers and not in-house stability data. This was last updated in January 2004 and contains information on 176 products. This currently unpublished document is available to other medicines information departments and may be available in the future on the UK Medicines Information website: www. ukmi.nhs.uk. In an attempt to provide clearer updated guidance on potential stability problems, we approached pharmaceutical manufacturers for their opinion on the stability of their products in compliance aids. original packs to compliance aids as it may be outside the terms of their product licence. For the majority of manufacturers any information they provide is based on anecdotal evidence or in-house studies as no formal studies would have been carried out.” Wyeth Laboratories requested its own disclaimer to be used as well, since it believed this would be a more accurate reflection of its products and is as follows: “The product information provided in this article has been provided by the marketing authorisation holders for these products.The marketing authorisation holders only recommend that their products are stored in accordance with the summary of product characteristics for each product and that storage of products in any other way is entirely at the pharmacist’s own risk.” These products are highlighted in the Table by an asterix (*) in the additional information column. Data presentation The Table now contains a list of 392 products in alphabetical order by generic name. Defined against each name is the brand name (if applicable), company, stability code and any other additional information relating to stability.The stability data have been classified into six groups according to the data received. Each group was allocated a code for ease of numbering in the Table linked to the extent of suitability for use in a compliance aid. Stability codes were allocated as follows: 1. Do not put into a compliance aid. 2. No stability data available, therefore company does not recommend putting in a compliance aid. (Refer to SPC for additional stability information.) 3. No stability data available, therefore company does not recommend putting in a compliance aid. Reason for concern is stated, eg, light-sensitive. Individual pharmacists must accept responsibility for putting in a compliance aid. Risks can be minimised by additional safeguards, eg, use of a black bag. 4. No stability data available, but it is probably suitable to put in a compliance aid. 5. Stability data available in an alternative container, but not necessarily in a compliance aid. 6. Stability data available which state that it is suitable to put in a compliance aid. The additional information that relates to stability is based on that received from the 21 January 2006 The Pharmaceutical Journal (Vol 276) 75 Data collection Fifty medical information departments of pharmaceutical companies in the UK were contacted by telephone during November and December 2002 and asked whether their solid oral dosage forms could be transferred to a compliance aid. No specific brand of aid was specified. Information in writing was received from all the pharmaceutical companies contacted and these data covered 243 products. A further exercise to confirm data was carried out in September 2004 and we now have information on 392 products (see Table). All but one company agreed to their data to be used in this article provided the following disclaimer is included and strongly emphasised: “It is important to note that the individual manufacturers do not endorse this practice of transferring medicines from the Claire Church, BPharm, MRPharmS, is community liaison pharmacist at Southmead Hospital, Bristol. Jane Smith, MSc,MRPharmS, is acting principal pharmacist, service development, at North Bristol NHS Trust (formerly senior pharmacist, patient services at Southmead Hospital). Correspondence to: Mrs Church (e-mail [email protected]). www.pjonline.com 248:124–6. formerly locum pharmacist (all at Southmead Hospital.These can be accessed online on the Electronic Medicines Compendium website at www. Katy Seager. The Table does not represent an exhaustive list and many companies were keen to remind professionals that the most suitable and current source of information regarding the stability of a medicinal product can be obtained direct from the medicine information department of the respective pharmaceutical companies. one fatal. requires companies to provide evidence of stability of the medicine in its original pack until its stated expiry date. The Medicines and Healthcare products Regulatory Agency (MHRA). 6. or chemical drug degradation of the product may occur. Some companies replied with more useful comments that included:“We do not have any relevant stability studies. The Society. They assume that all compliance aids will be stored at ambient temperature.medicines. there is a necessity for short-term stability data for all medicines. Bristol). — Buccal and mucosal products. Interface 2000. We hope to extend this to other products and publish the data. as either the formulation or the active component is sensitive to moisture.248:99. which are generally unstable. 5.uk. 2003. Since the publication of the leading article in The Pharmaceutical Journal in 19923 little appears to have changed in the availability of this stability information. SPCs may be a reference source for determining the stability of a product within the original packaging. and therefore cannot recommend the practice. which are unsuitable for packing in compliance aids owing to their hygroscopic nature. Medicines. based on the published and unpublished data reviewed: ■ Medicinal products which are likely to be susceptible to the effects of moisture. Alison Yeo. which may be unsuitable since they are formulated to dissolve and so are sensitive to moisture. eg. efficacy or palatability of any formulation that is stored outside its original container. This may be due to different production processes. Stability of medicines dispensed in compliance devices (letters). General exclusions Using the information obtained. medicines information.256:85. South West Medicines Information and Training. However. Many companies indicated that they do not have any stability data to support the storage in compliance aids. ■ Medicinal products that are susceptible to the effects of prolonged exposure to light ■ Medicinal products that are required to be kept refrigerated ■ Medicinal products the handling of which is likely to be harmful to individuals compliance aid. Eve Wood. Stability of medicinal products in compliance devices. to provide data on the stability of the product when redispensed into a compliance aid. It is essential that action is taken now to fill this information gap and so benefit patients and practice in the future. Omission of a medicine from the Table does not mean that the medicine is suitable for putting in a compliance aid. which issues product licences. References 1. different stability testing or one manufacturer being more cautious than another. light sensitivity. We would encourage manufacturers. including — Effervescent. if stored as recommended. 2. patients and carers are aware of these (see Panel above). This at least enables a pharmacist to make a judgement on whether to include or exclude a drug from a compliance aid in the absence of hard evidence. Most companies were sympathetic to pharmacists’ position and appreciate the fact that the use of compliance aids is becoming increasingly popular or indeed necessary and that it is obviously impractical to prevent the use of them. www. ■ We plan to work with medicines information pharmacists to ensure that the resources we and Pinderfields have developed are presented in a suitable format for web presentation.pjonline. and soluble products.248:174–5. It is impracticable to prevent the use of compliance aids until such data becomes available.6 It is also more difficult to remove the dose from a small area of packaging. none had had stability tests carried out on them within a compliance aid. As the practice of using compliance aids continues to grow. It was interesting that different companies sometimes offered conflicting advice for the same product. eg. Pharmaceutical Journal 1992. However.org. no 45.Articles manufacturers and is the best available from the resources at the time of compilation. formerly senior pharmacist. Blister-strip warning. ACKNOWLEDGEMENTS We thank the medicines information departments of the various pharmaceutical companies and also the following pharmacists for their help in compiling this article: Hazel Arnold. 3. but these tablets are generally stable and we are not aware of any specific reason why they should not be stored in a compliance aid for x number of days. Dealing with dosage aids (leading article). Ingress of moisture into the compliance aid may impair dispersal or dissolution properties of the product. this practice is avoided in our dispensary since the publication of a warning in The Pharmaceutical Journal which concerned two incidents. Walker R. when the patients concerned swallowed a whole blister resulting in intestinal perforation. This was carried out in various compliance aids at normal (35–50%) and high (up to 85%) humidity. Pharmaceutical Journal 1996. Several companies offered a solution to avoid removal from their packaging by suggesting cutting around the blister and putting the dosage form (still in the blister) into the 76 The Pharmaceutical Journal (Vol 276) 21 January 2006 Future research ■ We have initiated joint research with our regional quality assurance officer to carry out in-house stability testing of specific drugs in compliance aids that we routinely use. It is hoped that this collection of data in a compact format will provide some assistance in the interim. Discussion Out of 392 products investigated. when applying for a new product licence. 4. They cannot guarantee the bioavailability. London. Some stated that storage in such devices would be an unlicensed use of their product and as such would remain the responsibility of the pharmacist or physician. The licence only covers storage in the original packaging and transfer to any other container cannot be advocated without extensive stability testing being carried out. There are. — Significantly hygroscopic products. director. The survey carried out suggests that most solid oral dosage forms can be safely transferred to a compliance aid for a short period. Royal Pharmaceutical Society of Great Britain. Pharmaceutical Journal 1992. senior pharmacist.com . the stability of dispersible and enteric coated aspirin has been investigated. formerly patient services pharmacist. At the time of writing. in a dry environment and away from direct sunlight. however. ethics and practice: a guide for pharmacists (number 27). Conclusion This survey has revealed that although some information can be obtained from the pharmaceutical companies there is still a shortage of short-term stability data for the transfer of medication to compliance aids. quality assurance. we would suggest some general exclusions. and Richard Cattell.This information could be made available in the SPC. Pharmaceutical Journal 1992. omeprazole. hygroscopicity. with an ageing population and greater care in patient’s homes.This would be particularly useful for products that are unstable. both general and specific exceptions to this and it is important that pharmacists. dispersible. This will reduce the problems that arise when patients using compliance aids are transferred between primary and secondary care. more general guidelines for the transfer of solid oral dosage forms from original packs to compliance aids have been written. ■ We have liaised with the other two Bristol hospitals and the local primary care trusts with the aim of developing a common policy. Most companies will not recommend transferring medicines from original packs to compliance aids due to the absence of stability studies. Stability of medicines in compliance aids and monitored dose systems.” Even more useful replies were from the companies that provided information on the chemical and physical properties of their drug. light sensitive over time Probably stable for 6 months Protect from light Probably stable for 4 weeks Should only be dispensed in glass bottles Protect from moisture Store in dark Probably stable for 7 days Protect from light Citalopram Clarithromycin Clarithromycin XL Clobazam Clomethiazole Clomipramine Clonazepam Clopidogrel Cloral Betaine Clozapine Co-amilofruse 5/40 Co-amilofruse Co-amilofruse Co-amilozide Co-beneldopa Co-beneldopa dispersible Co-careldopa Cipramil Klaricid Klaricid Frisium Heminevrin Anafranil Rivotril Plavix Welldorm Clozaril Lasoride Madopar Madopar dispersible Sinemet Lundbeck Abbott Abbott Sanofi Aventis AstraZeneca Cephalon UK Roche SS Alphashow Novartis Generics (UK) Borg CP APS Roche Roche BMS 4 3 2 4 1 2 3 2 4 2 4 3 2 2 4 5 1 Probably stable for 14 days Stable for at least 14 days Powder is hygroscopic Generic name Acarbose Acetazolamide Aciclovir Aciclovir Aciclovir dispersible Alendronate 5mg Brand name Glucobay Diamox / SR Zovirax Zovirax dispersible Fosamax Company Bayer Goldshield GSK Pfizer GSK MSD Code 4 2 2 2 1 5 Additional information Should be stable for 7 days Dispersible tablet Stable for 3 months at 40C and 75% relative humidity Alendronate 10mg/70mg Fosamax Alfacalcidol One Alpha MSD Leo 2 1 Moisture sensitive. based on information provided by manufacturers (acarbose to co-careldopa) Brand name Buspar Cabaser Dostinex Cacit Didronel PMO Probably stable for 7 days Should be stored with desiccant Effervescent tablet is moisture sensitive Cacit is moisture sensitive Company BSM Pfizer Pfizer P&G P&G Code 2 4 1 1 1 Additional information www.The stability of drugs in compliance aids. must be protected from light Ethanol vaporises out of the capsule when out of the original packaging Not known to be hygroscopic May absorb a small amount of water over time.pjonline.com Amias Acepril Capoten Acezide Capozide BMS 2 Susceptible to moisture Protect from light Probably stable for up to 4 weeks Sensitive to moisture AstraZeneca BMS BMS BMS 2 2 2 2 Generic name Buspirone Cabergoline Cabergoline Calcium carbonate Calcium carbonate and etidronate Candesartan Captopril Captopril Captopril/ hydrochlorothiazide Captopril/ hydrochlorothiazide Carbamazepine Carbenoxolone sodium Carvedilol Cefaclor Cefaclor MR Cefadroxil Cefprozil Cefradine Celecoxib Chlordiazepoxide Chloroquine phosphate/ proguanil HCl Chlorpromazine Tegretol / Retard Pyrogastrone Eucardic Distaclor Distaclor MR Baxan Cefzil Velosef Celebrex Librium Avloclor/Paludrine Largactil Neoral Stugeron/Forte Modalim Ciproxin Hawgreen Novartis Janssen-Cilag SS Bayer 3 1 2 2 1 Cephalon UK SS Roche Lilly Lilly BMS BMS BMS Pfizer Valeant AstraZeneca 1 2 3 4 1 2 2 1 2 2 2 Powder is hygroscopic Ciclosporin Cinnarizine Ciprofibrate Ciprofloxacin Can cause contact dermatitis when handled (wear gloves). can become sticky out of original packaging and congeal with other tablets in the compliance aid Xatral / XL Zyloric Moduretic SS GSK BMS 2 2 2 Hygroscopic Disintegrates in the presence of small amounts of water Probably ok for short term storage in a compliance aid Hygroscopic Hygroscopic Not suitable as sensitive to atmospheric moisture Probably not suitable as sensitive to moisture Potential to be hygroscopic Disintegrates in bright sunshine Protect from moisture Articles Soluble tablet Alfuzosin Allopurinol Amiloride/ hydrochlorothiazide Amiodarone Amiodarone Amisulpride Amlodipine Amphotericin Anastrazole Apomorphine Aripiprazole Aspirin Aspirin Aspirin Aspirin EC Atenolol Atenolol Atenolol/chlortalidone Atenolol/co-amilozide Atenolol/nifedipine Atazanavir sulphate Atorvastatin Auranofin Baclofen Baclofen Bambuterol HCl Benperidol Beta-cardone Betahistine Betamethasone Betamethasone Bexarotene Bicalutamide Bisoprolol Bisoprolol Bisoprolol Bumetanide Buprenorphine HCl Buprenorphine HCl Cordarone SS Alpharma Solian SS Istin Pfizer Fungilin BSM Arimidex AstraZeneca Uprima Abbott Abilify BSM Angettes BSM Alpharma Nu-Seals Lilly Caprin Pinewood Tenormin AstraZeneca CP Tenoretic/Tenoret 50 AstraZeneca Kalten AstraZeneca Tenif AstraZeneca Reyataz BSM Lipitor Pfizer Ridaura Yamanouchi Lioresal Cephalon UK APS Bambec AstraZeneca Benquil Hansam Sotalol Celltech Serc Solvay Betnelan Celltech Betnesol Celltech Targretin Zeneus Pharma Casodex AstraZeneca Cardicor Merck APS IVAX Burinex Leo Temgesic RB Subutex RB 2 2 1 1 2 4 2 1 1 1 2 1 2 2 2 2 2 2 3 2 1 2 2 2 2 2 2 1 4 2 2 2 4 4 2 2 21 January 2006 The Pharmaceutical Journal (Vol 276) 77 Probably stable for 7 days . plastic dispensing bottle Protect from light Probably stable for 8 days Dipyridamole MR/ aspirin Dipyridamole Disopyramide Docusate sodium Domperidone Domperidone/ paracetamol Donepezil Dosulepin tablets and capsules Dosulepin Doxazosin Doxazosin Aricept - Pfizer Generics (UK) 4 4 Probably stable for 14 days Probably stable for 7 days Prothiaden Cardura Cardura XL Abbott Pfizer Pfizer 2 2 1 Not recommended for inclusion in compliance aid.78 Brand name Erymax Erythromid Erythroped A Company Celltech Zeneus Pharma Abbott Abbott Code Additional information 2 4 3 Protect from light 2 Probably stable for 6 months Stable for 6 months at 25C and relative humidity of 60% Generic name Ergometrine Erythromycin Erythromycin BP Erythromycin ethylsuccinate Erythromycin stearate Escitalopram Esomeprazole Etidronate disodium Ethamsylate Ethinylestradiol Etoposide Felodipine Ferrous fumarate/ folic acid Ferrous sulphate Erythocin Cipralex Nexium Didronel Dicynene Vepesid Plendil Pregaday Cytotoxic Ferrograd Ferrograd C Ferrograd folic Proscar MSD Abbott 2 1 Women should not handle crushed or broken tablets when they are or potentially may be pregnant (if the dispenser and/or carer is male or not pregnant the stability code can be changed to 2) GSK Pfizer BMS SS 2 4 2 2 Abbott Abbott 2 2 Alpharma 4 Abbott Lundbeck AstraZeneca P&G SS Celltech BMS AstraZeneca Celltech 2 4 5 2 2 2 1 2 2 Probably stable for maximum of 14 days (could taint other tablets) Ferrous sulphate Ferrous sulphate/ sodium ascorbate Ferrous sulphate/ folic acid Finasteride Floxapen Diflucan Florinef Moditen Probably stable for up to 4 weeks Probably stable for 4 weeks Probably stable for 4 weeks Probably stable for 4 weeks Protect from light Probably stable for 8 days Flucloxacillin Fluconazole Fludrocortisone Fluphenazine HCl Fluphenazine/ nortriptyline Fluoxetine Flupentixol Flupentixol Flurazepam Flurbiprofen Flutamide Fosinopril Furosemide Furosemide Furosemide/potassium Gabapentin Gemfibrozil Gliclazide Glipizide Gliquidone Haloperidol Hydroxycarbamide Hydroxychloroquine Hydroxyzine Motival Prozac Depixol Fluanxol Dalmane Froben/SR Drogenil Staril Lasikal Neurontin Lopid Diamicron/MR Glibenese Glurenorm Hydrea Plaquenil Atarax SS Lilly Lundbeck Lundbeck Valeant Abbott Schering Plough BMS Alpharma CP Borg Pfizer Pfizer Servier Pfizer SS IVAX BMS SS Pfizer 2 4 4 4 2 2 2 2 4 2 3 2 2 4 2 2 4 1 2 4 Probably stable for 7 days Cytotoxic Probably stable for 7 days The stability of drugs in compliance aids. SPC states “must be stored in the original package” Doxepin Efavirenz Enalapril Sinequan Sustiva Innovace Pfizer BMS MSD 2 2 1 May hydrolyse at high temperature and in the presence of moisture. based on information provided by manufacturers (co-careldopa to hydroxyzine) Generic name Co-careldopa Co-careldopa Brand name Sinemet CR Sinemet 110/250 Company BMS BMS Articles The Pharmaceutical Journal (Vol 276) 21 January 2006 Normax Septrin Valoid Danol Dantrium Ledermycin Neoclarityn Dexedrine Eudemine Voltarol Arthrotec Code Additional information 1 Powder is hygroscopic 1 Blue dye can fade on light exposure. also moisture will cause levodopa to turn black on prolonged exposure Celltech 2 GSK 2 CP 2 Celltech 2 Amdipharm 3 Light sensitive SS 2 P&G 2 Goldshield 2 Schering Plough 4 Unlikely to be hygroscopic Organon 4 Unlikely to be any issues Celltech 2 Celltech 2 Novartis 2 Pfizer 1 Misoprostol is extremely moisture sensitive and may degrade Hygroscopic See Calcium carbonate and etidronate Probably stable for 14 days Co-danthrusate Co-trimoxazole Codeine phosphate Colchicine Cyclizine Danazol Dantrolene sodium Demeclocycline Desloratidine Dexamethasone Dexamfetamine sulphate Diazoxide Diclofenac EC/SR/Retard Diclofenac and misoprostol Didanosine chewable Didanosine EC Didronel PMO Digitoxin Digoxin Diltiazem hydrochloride Diltiazem Diltiazem Diltiazem Diltiazem Dipyridamole MR Videx Videx EC Lanoxin Dilzem Slozem Adizem SR/XL Angitil SR/XL Tildiem/LA/Retard Persantin Retard BMS BMS P&G Celltech GSK Zeneus Pharma Merck Napp Trinity SS BI 1 2 1 2 4 4 2 2 4 2 5 Probably stable for 4 weeks Asasantin Retard BI 5 Persantin Rythmodan Dioctyl Motilium Domperamol BI Borg Schwartz SS Servier 3 2 4 2 4 Moisture sensitive. stable for 30 days out of the original container.com Ergocalciferol - Celltech 2 .pjonline. plastic dispensing bottle Stable for 30 days out of the original container. eg. eg. 10% loss of potency occurred when exposed to 40C and 75% humidity for 13 weeks www. The stability of drugs in compliance aids. based on information provided by manufacturers (ibuprofen to paracetamol/codeine) Brand name Flagyl Minocin MR Loniten Zispin Hygroscopic. packaged in high density polyethylene bottles with a dessicant Creon Solpadol Solvay Alpharma SS SS 2 4 2 1 Probably stable for up to 28 days Pancreatin Paracetamol Paracetamol/codeine caplet/capsules Paracetamol/codeine effervescent tablets Brand name Brufen/Retard Natrilix/SR Hexopal Aprovel Company Abbott Servier SS BMS Code Additional information 2 4 Probably stable for 8 days 2 2 Probably stable for up to 14 days Probably stable for 7 days Generic name Ibuprofen Indapamide Inositol nicotinate Irbesartan Irbesartan /hydrochlorothiazide Isoniazid Isosorbide mononitrate Isosorbide mononitrate Isosorbide mononitrate Isosorbide mononitrate Isosorbide mononitrate Isosorbide mononitrate Ketoprofen Ketoprofen Ketoprofen MR Labetolol hydrochloride Lamivudine Lamotrigine Lansoprazole CoAprovel Cedocard Retard Elantan LA Imdur Monomax SR/XL Ketocid Orudis Oruvail Trandate Epivir Lamictal Zoton BMS Celltech Alpharma IVAX Pfizer Schwartz AstraZeneca Trinity Trinity Hawgreen Hawgreen Celltech GSK GSK Wyeth 2 2 4 4 2 2 5 4 4 3 3 2 2 2 4 Stable for one month Probably stable for 4 weeks Probably stable for 4 weeks Must be protected from light Must be protected from light Zoton FasTab Wyeth 1 Probably stable for up to 4 weeks in a compliance aid which offers a barrier against moisture* Highly moisture sensitive* Zestril Carace Carace plus APS Alpharma AstraZeneca BMS BMS 2 2 2 2 2 Zestoretic AstraZeneca 2 Priadel Imodium Kaletra Cozaar Farlutal SS Janssen-Cilag Abbott MSD Pfizer 4 1 2 2 2 Probably stable for 7 days Moisture sensitive and could change colour Articles Tablet coating is moisture and light sensitive Cytotoxic Packaged with a desiccant Lansoprazole orodispersible Levothyroxine Levothyroxine Lisinopril Lisinopril Lisinopril/ hydrochlorothiazide Lisinopril/ hydrochlorothiazide Lithium Loperamide Lopinavir/ritonavir Losartan Medroxyprogesterone acetate Medroxyprogesterone acetate Megestrol Memantine HCl Meloxicam Mesalazine Methionine Metformin Methotrexate Methylphenidate HCl Methylphenidate HCl Methylphenidate HCl Metolazone Metoprolol tartrate 21 January 2006 The Pharmaceutical Journal (Vol 276) 79 Provera Megace Ebixa Mobic Asacol Glucophage Maxtrex Ritalin Concerta XL Equasym Metenix 5 Betaloc SA Pfizer BMS Lundbeck BI P&G Celltech Merck Pfizer Cephalon UK Janssen-Cilag Celltech Borg AstraZeneca 2 2 2 4 1 2 2 1 2 1 2 3 2 Protect from light . Stable for at least 7 days in a dry environment Very light sensitive Very light sensitive and will significantly degrade very quickly. can write days of the week on lidding paper of each tablet pouch Moisture sensitive and may degrade Company Hawgreen Wyeth Pfizer Organon Code 3 4 2 1 Additional information Must be protected from light Probably stable for 7 days* www. as an alternative.pjonline.com Generic name Metronidazole Minocycline Minoxidil Mirtazapine orodispersible Misoprostol Modafinil Morphine sulphate Moxifloxacin Nadolol Naftidofuryl Nalidixic acid Naltrexone Naproxen and misoprostol Nevirapine Nicardipine Nicardipine Nicorandil Nifedipine Cytotec Provigil MST Continus Avelox Corgard Praxilene Negram Nalonex Napratec Should be stable for 7 days BI Yamanouchi Yamanouchi Sanofi Aventis Bayer Bayer 1 4 2 3 5 1 Pfizer Cephalon UK Napp Bayer SS Merck SS BMS Pfizer 1 2 2 4 2 2 2 2 2 Protect from light. moisture can affect release mechanism Should be stable for 7 days Probably stable for up to 4 weeks 2 4 2 4 2 1 4 Nifedipine Nifedipine Nimodipine Nitrazepam Nizatidine Norethisterone Nystatin Olanzapine Coracten SR/XL Nimotop Mogadon Axid Utovlan Nystan Zyprexa Celltech Bayer Valeant Lilly Pfizer BMS Lilly Viramune Cardene Cardene SR Ikorel Adalat Retard and capsules Adalat LA Olanzapine Velotabs Zyprexa Velotabs Lilly Celltech Generics (UK) AstraZeneca 1 2 1 5 Hygroscopic Stable for 14 days at room temperature (25–30C) and relative humidity up to 75% Stable for 3 months at 25C and relative humidity of 60% Powder is hygroscopic Probably stable for up to 4 weeks. wear gloves if breaking or dividing the tablets due to potential contact dermatitis Particularly fragile/brittle — may disintegrate due to moisture in the air Olsalazine sodium Dipentum tablets and capsules Omeprazole capsules Omeprazole capsules Losec Omeprazole MUPS Orphenadrine Oxybutynin Oxybutynin Oxybutynin XL Losec MUPS Disipal Cystrin Ditropan Lyrinel XL AstraZeneca Yamanouchi SS SS Janssen-Cilag 5 2 2 2 1 Hygroscopic. sensitive to light. hydroxylates and becomes unstable with water Zanaflex Detrusitol/ XL Topamax Zydol Gopten Cyklokapron Molipaxin Surmontil De-Noltab Bextra Epilim Epilim chrono Depakote Diovan Zeneus Pharma Pfizer Janssen-Cilag Pfizer Abbott Pfizer Sanofi Aventis Sanofi Aventis Yamanouchi Pfizer SS SS SS Novartis 4 2 1 2 2 2 2 2 2 2 1 1 2 2 Hygroscopic Hygroscopic Tetrabenazine Theophylline Theophylline Theophylline Theophylline/ephedrine Thioridazine Thiamine Tiagabine Tiludronic acid Timolol maleate Timolol maleate/ bendroflumethiazide Tizanidine HCl Tolterodine Topiramate Tramadol Trandolapril Tranexamic acid Trazodone Trimipramine Tri-potassium di-citratobismuthate Valdecoxib Valproate sodium EC/ crushable tablets Valproate sodium chrono Valproic acid Valsartan The stability of drugs in compliance aids.com Selegiline HCl Senna (sennosides) Sertindole Sertraline Zelapar Senokot Serdolect Lustral Zeneus Pharma 1 Reckitt Benckiser 1 Lundbeck 3 Pfizer 4 Hygroscopic Probably stable for 4 weeks Store in the dark Probably stable for 3 months out of the refrigerato. based on information provided by manufacturers (paracetamol/metoclopramide to valsartan) Generic name Paracetamol/ metoclopramide Paroxetine Penicillamine Pergolide Brand name Paramax Company SS Code Additional information 2 Seroxat Distamine Celance GSK Lilly Lilly 2 2 1 Articles The Pharmaceutical Journal (Vol 276) 21 January 2006 Perindopril Perindopril/indapamide Phenytoin Piroxicam Piroxicam dispersible Potassium chloride Coversyl Coversyl Plus Epanutin/Infatab Feldene Feldene Melt Slow K Servier Servier Pfizer Pfizer Pfizer Alliance 4 4 2 2 1 4 Unstable — light sensitive and extremely hygroscopic (notably the 50µg strength) Probably stable for 8 days Probably stable for 8 days Moisture sensitive May absorb water. store in the dark Hygroscopic Can absorb moisture Very light sensitive .pjonline.80 Brand name Reductil Zocor Beta-cardone Sotacor Lasilactone Company Abbott MSD Celltech BMS IVAX Alpharma Borg Code Additional information 2 2 2 2 3 Protect from light 2 3 Protect from light Stable for 3 months at 30C and 75% humidity Known to be light labile Sensitive to light Cytotoxic Generic name Sibutramine Simvastatin Sotalol Sotalol Spironolactone Spironolactone Spironolactone/ furosemide Stavudine Sulfasalazine Sulpiride Sulpiride Tacrolimus Tamoxifen Tamoxifen Tamoxifen Tamsulosin Tegafur with uracil Terazosin Terbinafine Terbutaline sulphate Testosterone Zerit Salazopyrin/EN/EC Dolmatil Sulpitil Prograf Nolvadex Flomax SR Uftoral Hytrin Lamisil Bricanyl Restandol BMS Pfizer SS Pfizer Fujisawa AstraZeneca APS Generics (UK) Yamanouchi BMS Abbott Novartis AstraZeneca Organon 2 2 2 2 5 3 2 3 2 1 2 2 2 1 Very sensitive to moisture and becomes “sticky” if removed from packaging Xenazine 25 Slo-Phyllin Uniphyllin Nuelin SA Franol/Plus Melleril Benerva Gabitril Skelid Betim Prestim Cambridge Merck Napp 3M SS Novartis Roche Cephalon UK SS Valeant Valeant 2 2 2 2 2 2 4 2 2 2 2 Hygroscopic. probably stable in an airtight compliance aid for 14 days Lipostat Hypovase Deltacortril Buccastem BMS 2 Pfizer 2 APS 2 Pfizer 2 Reckitt Benckiser 2 Store in a brown bottle with a desiccant Probably stable for up to 7 days Arythmol Inderal/Half Inderal Mestinon Seroquel Accupro Kinidin Pariet Evista Tritace Abbott AstraZeneca Celltech Valeant AstraZeneca Pfizer AstraZeneca Alpharma Janssen-Cilag Lilly Sanofi Aventis 2 2 2 1 4 2 2 4 1 2 2 Probably stable for up to 7 days Hygroscopic Pravastatin Prazosin Prednisolone Prednisolone EC Prochlorperazine maleate Propafenone Propranolol HCl Propylthiouracil Pyridostigmine Quetiapine Quinapril Quinidine bisulphate Quinine sulphate Rabeprazole Raloxifene Ramipril tablets and capsules Ranitidine Ranitidine Reboxetine Ribavirin Risedronate sodium Risperidone Zantac Edronax Rebetol Actonel Risperdal Generics (UK) GSK Pfizer Schering Plough P&G Janssen-Cilag 1 1 2 2 2 2 Hygroscopic and may turn brown Hygroscopic and degrades in the presence of water Ritonavir Ropinirole Norvir Requip Abbott GSK 2 5 Not known to be hygroscopic or need a drying agent during storage Refrigeration by patient not required if used within 30 days Stable for up to 28 days below 25C and at 60% relative humidity Rosuvastatin Salbutamol Salbutamol Saquinavir Saquinavir Crestor Volmax Ventmax SR Invirase Fortovase AstraZeneca A&H/(GSK) Trinity Roche Roche 2 1 4 3 3 www. Merck Sharp & Dohme.pjonline. based on information provided by manufacturers (vancomycin to zuclopenthixol) www. Advertisement Articles 21 January 2006 The Pharmaceutical Journal (Vol 276) 81 .The stability of drugs in compliance aids. Stability data available in an alternative container. 4. P&G. MSD. GSK. 5. KEY TO MANUFACTURERS: BI. No stability data available. No stability data available. eg. Bristol-Myers Squibb. *The product information provided in this article has been provided by the marketing authorisation holders for these products. (Refer to SPC for additional stability information. but not necessarily in a compliance aid. use of a black bag. Reason for concern is stated. The marketing authorisation holders only recommend that their products are stored in accordance with the summary of product characteristics for each product and that storage of products in any other way is entirely at the pharmacist’s own risk. 2. therefore company does not recommend putting in a compliance aid. Boehringer Ingelheim. BSM. GlaxoSmithKline. therefore company does not recommend putting in a compliance aid. Sanofi Synthelabo Protect from light 2mg stable for 14 days. Risks can be minimised by additional safeguards. Stability data available which state that it is suitable to put in a compliance aid. Procter & Gamble. light-sensitive.) 3. For the majority of manufacturers any information they provide is based on anecdotal evidence or in-house studies as no formal studies would have been carried out. 6. eg. other strengths stable for 4 weeks DISCLAIMERS: It is important to note that the individual manufacturers do not endorse the practice of transferring medicines from the original packs to compliance aids as it may be outside the terms of their product licences. No stability data available. Do not put into a compliance aid. SS. but it is probably suitable to put in a compliance aid. Individual pharmacists must accept responsibility for putting in a compliance aid.com Generic name Vancomycin Vardenafil Venlafaxine Venlafaxine XL Verapamil HCl Verapamil HCl Brand name Vancocin Matrigel Levitra Efexor Efexor XL Univer Securon/SR/ Half Securon SR Tarka Company Lilly Bayer Wyeth Wyeth Zeneus Pharma Abbott Code 4 4 1 4 4 2 Additional information Probably stable for up to 4 weeks Should be stable for 7 days Moisture sensitive* Probably stable for 7 days* Key to stability codes Abbott 2 Verapamil HCl/ trandolapril Warfarin Zafirlukast Zaleplon Zidovudine Zidovudine/lamivudine Zolmitriptan Zolpidem Zopiclone Zopiclone Zuclopenthixol Accolate Sonata Retrovir Combivir Zomig Stilnoct Zimovane Clopixol Goldshield AstraZeneca Wyeth GSK GSK AstraZeneca SS Sanofi Aventis IVAX Lundbeck 2 5 2 2 2 2 2 2 3 4 Stable for 30 days at 60-80% relative humidity * 1.