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 longer than eight weeks” and that “certain original packs to compliance aids as it may be both primary and secondary care over re- medications should not be placed in moni- outside the terms of their product licence. For Tcent years. Compliance aids aim to act as tored dosage systems.These include efferves- the majority of manufacturers any informa- a reminder for patients to take their medi- cent tablets, dispersible tablets, buccal tion they provide is based on anecdotal evi- cines, enabling them to manage their own tablets, sublingual tablets, significantly hygro- dence or in-house studies as no formal studies often complex and confusing drug regimens. scopic preparations and solid dose cytotoxic would have been carried out.” They also act as a visual prompt for carers, in- preparations.” Wyeth Laboratories requested its own dis- dicating that patients have taken their medi- A general article by Roger Walker in The claimer to be used as well, since it believed cines, or at least removed them from the Pharmaceutical Journal in 19922 contained in- this would be a more accurate reflection of its device. formation on around 70 products from 53 products and is as follows: “The product in- The use of these aids involves the transfer pharmaceutical manufacturers. The leading formation provided in this article has been of medicines from the manufacturer’s original article in the same journal discussed the lack provided by the marketing authorisation packaging to the compliance aid. The origi- of data and concluded: “Manufacturers and holders for these products.The marketing au- nal packaging is designed to protect the con- regulatory authorities urgently need to catch thorisation holders only recommend that tents to appropriate pharmacopoeial and up with current practice.”3 In response to their products are stored in accordance with quality standards for a variety of criteria, eg, these articles a series of letters appeared a few the summary of product characteristics for water vapour transmission, as required in the weeks later.4 each product and that storage of products in product licence. However, the compliance A medicines and prescribing bulletin for any other way is entirely at the pharmacist’s aid cannot guarantee the same level of health care professionals in East Lancashire own risk.”These products are highlighted in protection. published data on approximately 30 products the Table by an asterix (*) in the additional Many systems are not disposable and are in November 2000.5 information column. frequently reused without cleaning.The haz- The medicines information department at ards associated with physical, chemical and Pinderfields General Hospital has collated Data presentation microbiological cross-contamination could data that are largely derived from pharmaceu- The Table now contains a list of 392 products be a major risk factor. All other dispensing tical manufacturers and not in-house stability in alphabetical order by generic name. containers are designed for single use. data. This was last updated in January 2004 Defined against each name is the brand name Compliance aids have limited available and contains information on 176 products. (if applicable), company, stability code and space for each dose, are not airtight and offer This currently unpublished document is any other additional information relating to less moisture and light protection than origi- available to other medicines information de- stability.The stability data have been classified nal packs. Doubts are raised as to the stability partments and may be available in the future into six groups according to the data re- of medicines that have been transferred to on the UK Medicines Information website: ceived. Each group was allocated a code for compliance aids: is there a deterioration in www. ukmi.nhs.uk. ease of numbering in the Table linked to the quality and can this result in a reduction of In an attempt to provide clearer updated extent of suitability for use in a compliance efficacy to an unacceptable level? guidance on potential stability problems, we aid. Stability codes were allocated as follows: Despite the increased dispensing of medi- approached pharmaceutical manufacturers cines in this way,guidance on their stability in for their opinion on the stability of their 1. Do not put into a compliance aid. these systems is limited and little new infor- products in compliance aids. 2. No stability data available, therefore com- mation has been published in recent years. pany does not recommend putting in a Certain products are particularly unsuitable Data collection compliance aid. (Refer to SPC for addi- for transferring into compliance aids, but Fifty medical information departments of tional stability information.) even this information is often not readily pharmaceutical companies in the UK were 3. No stability data available, therefore com- available. contacted by telephone during November pany does not recommend putting in a The Royal Pharmaceutical Society, in it and December 2002 and asked whether their compliance aid. Reason for concern is “Medicines, ethics and practice” guide (sec- solid oral dosage forms could be transferred stated, eg, light-sensitive. Individual phar- tion 3.4.7) says that “medicines should not be to a compliance aid. No specific brand of aid macists must accept responsibility for put- left in sealed monitored dosage systems for was specified. ting in a compliance aid. Risks can be Information in writing was received from minimised by additional safeguards, eg, use Claire Church, BPharm, MRPharmS, is all the pharmaceutical companies contacted of a black bag. community liaison pharmacist at and these data covered 243 products. A fur- 4. No stability data available, but it is proba- Southmead Hospital, Bristol. ther exercise to confirm data was carried out bly suitable to put in a compliance aid. Jane Smith, MSc,MRPharmS, is acting in September 2004 and we now have infor- 5. Stability data available in an alternative principal pharmacist, service development, mation on 392 products (see Table). container, but not necessarily in a compli- at North Bristol NHS Trust (formerly senior All but one company agreed to their data ance aid. pharmacist, patient services at Southmead to be used in this article provided the follow- 6. Stability data available which state that it is Hospital). ing disclaimer is included and strongly em- suitable to put in a compliance aid. phasised: “It is important to note that the Correspondence to: Mrs Church (e-mail individual manufacturers do not endorse this The additional information that relates to [email protected]). practice of transferring medicines from the stability is based on that received from the www.pjonline.com 21 January 2006 The Pharmaceutical Journal (Vol 276) 75 Articles manufacturers and is the best available from are unstable.This information could be made the resources at the time of compilation. General exclusions available in the SPC. It is essential that action The Table does not represent an exhaustive is taken now to fill this information gap and list and many companies were keen to remind Using the information obtained, more general so benefit patients and practice in the future. professionals that the most suitable and cur- guidelines for the transfer of solid oral dosage rent source of information regarding the sta- forms from original packs to compliance aids have Conclusion bility of a medicinal product can be obtained been written. They assume that all compliance This survey has revealed that although some direct from the medicine information depart- aids will be stored at ambient temperature, in a information can be obtained from the phar- ment of the respective pharmaceutical dry environment and away from direct sunlight. maceutical companies there is still a shortage companies. However, we would suggest some general of short-term stability data for the transfer of SPCs may be a reference source for deter- exclusions, based on the published and medication to compliance aids. Since the mining the stability of a product within unpublished data reviewed: publication of the leading article in The the original packaging.These can be accessed Pharmaceutical Journal in 19923 little appears to online on the Electronic Medicines Comp- ■ Medicinal products which are likely to be have changed in the availability of this stabil- endium website at www.medicines.org.uk. susceptible to the effects of moisture, ity information. It is impracticable to prevent Omission of a medicine from the Table including the use of compliance aids until such data be- does not mean that the medicine is suitable — Effervescent, dispersible, and soluble comes available. It is hoped that this collec- for putting in a compliance aid. products, which are unsuitable for packing in tion of data in a compact format will provide compliance aids owing to their hygroscopic some assistance in the interim. Discussion nature. Ingress of moisture into the Out of 392 products investigated, none had compliance aid may impair dispersal or ACKNOWLEDGEMENTS We thank the had stability tests carried out on them within dissolution properties of the product, or medicines information departments of the a compliance aid. The Medicines and chemical drug degradation of the product may various pharmaceutical companies and also Healthcare products Regulatory Agency occur. the following pharmacists for their help in (MHRA), which issues product licences, re- — Buccal and mucosal products, which may compiling this article: Hazel Arnold, senior quires companies to provide evidence of sta- be unsuitable since they are formulated to pharmacist, quality assurance; Alison Yeo, for- bility of the medicine in its original pack dissolve and so are sensitive to moisture. merly senior pharmacist, medicines informa- until its stated expiry date, if stored as recom- — Significantly hygroscopic products, which tion; Eve Wood, formerly patient services mended. The licence only covers storage in are generally unstable, as either the pharmacist; Katy Seager, formerly locum the original packaging and transfer to any formulation or the active component is pharmacist (all at Southmead Hospital, other container cannot be advocated without sensitive to moisture. Bristol); and Richard Cattell, director, South extensive stability testing being carried out. ■ Medicinal products that are susceptible to the West Medicines Information and Training. Most companies will not recommend effects of prolonged exposure to light transferring medicines from original packs to ■ Medicinal products that are required to be kept compliance aids due to the absence of stabil- refrigerated References ity studies. They cannot guarantee the ■ Medicinal products the handling of which is 1. Royal Pharmaceutical Society of Great Britain. Medicines, bioavailability, efficacy or palatability of any likely to be harmful to individuals ethics and practice: a guide for pharmacists (number 27). formulation that is stored outside its original London; The Society; 2003. container. Many companies indicated that 2. Walker R. Stability of medicinal products in compliance they do not have any stability data to support compliance aid. However, this practice is devices. Pharmaceutical Journal 1992;248:124–6. 3. Dealing with dosage aids (leading article). Pharmaceutical the storage in compliance aids, and therefore avoided in our dispensary since the publica- Journal 1992;248:99. cannot recommend the practice. Some stated tion of a warning in The Pharmaceutical Journal 4. Stability of medicines dispensed in compliance devices that storage in such devices would be an un- which concerned two incidents, one fatal, (letters). Pharmaceutical Journal 1992;248:174–5. licensed use of their product and as such when the patients concerned swallowed a 5. Stability of medicines in compliance aids and monitored would remain the responsibility of the phar- whole blister resulting in intestinal perfora- dose systems. Interface 2000; no 45. macist or physician. tion.6 It is also more difficult to remove the 6. Blister-strip warning. Pharmaceutical Journal 1996;256:85. Most companies were sympathetic to dose from a small area of packaging. pharmacists’ position and appreciate the fact It was interesting that different companies that the use of compliance aids is becoming sometimes offered conflicting advice for the Future research increasingly popular or indeed necessary and same product, eg, omeprazole. This may be ■ We have initiated joint research with our that it is obviously impractical to prevent the due to different production processes, differ- regional quality assurance officer to carry out use of them. Some companies replied with ent stability testing or one manufacturer in-house stability testing of specific drugs in more useful comments that included:“We do being more cautious than another. compliance aids that we routinely use. At the not have any relevant stability studies, but The survey carried out suggests that most time of writing, the stability of dispersible and these tablets are generally stable and we are solid oral dosage forms can be safely trans- enteric coated aspirin has been investigated. not aware of any specific reason why they ferred to a compliance aid for a short period. This was carried out in various compliance should not be stored in a compliance aid for There are, however, both general and specific aids at normal (35–50%) and high (up to x number of days.” exceptions to this and it is important that 85%) humidity. We hope to extend this to other Even more useful replies were from the pharmacists, patients and carers are aware of products and publish the data. companies that provided information on the these (see Panel above). ■ We have liaised with the other two Bristol chemical and physical properties of their As the practice of using compliance aids hospitals and the local primary care trusts drug, eg, hygroscopicity, light sensitivity.This continues to grow,with an ageing population with the aim of developing a common policy. at least enables a pharmacist to make a judge- and greater care in patient’s homes, there is a This will reduce the problems that arise when ment on whether to include or exclude a necessity for short-term stability data for all patients using compliance aids are transferred drug from a compliance aid in the absence of medicines. between primary and secondary care. hard evidence. We would encourage manufacturers, ■ We plan to work with medicines information Several companies offered a solution to when applying for a new product licence, to pharmacists to ensure that the resources we avoid removal from their packaging by sug- provide data on the stability of the product and Pinderfields have developed are presented gesting cutting around the blister and putting when redispensed into a compliance aid.This in a suitable format for web presentation. the dosage form (still in the blister) into the would be particularly useful for products that

76 The Pharmaceutical Journal (Vol 276) 21 January 2006 www.pjonline.com Articles gloves); must be protected from light original packaging sensitive over time and etidronate hydrochlorothiazide hydrochlorothiazide proguanil HCl dispersible dispersible Generic nameBuspironeCabergolineCabergoline Brand nameCalcium carbonate Calcium carbonate Company Buspar Cacit Cabaser DostinexCandesartan Didronel PMO CodeCaptopril Additional information Captopril P&G BSM PfizerCaptopril/ P&G Pfizer AmiasCaptopril/ 1 Acepril 4 2 1 Capoten 1Carbamazepine Cacit is moisture sensitive Acezide stable for 7 days Probably AstraZenecaCarbenoxolone sodium Effervescent tablet is moisture sensitive Should be stored with desiccant PyrogastroneCarvedilol 2 / Retard Capozide Tegretol BMSCefaclor BMS Cephalon UK Cefaclor MR SS BMS 1Cefadroxil BMSCefprozil 2 Eucardic Susceptible to moisture 2 Cefradine 2 Distaclor MR Distaclor Celecoxib 2 Chlordiazepoxide 2 Baxan RocheChloroquine phosphate/ Lilly Avloclor/Paludrine Lilly Cefzil AstraZeneca Librium VelosefChlorpromazine Celebrex 2 3 BMS 1 4 Largactil from light Protect BMS Valeant BMS Sensitive to moisture Pfizer stable for up to 4 weeks Probably 2 2 Hawgreen 2 1 2 3 is hygroscopic Powder Can cause contact dermatitis when handled (wear CiclosporinCinnarizineCiprofibrateCiprofloxacin NeoralCitalopram Stugeron/Forte ModalimClarithromycin Ciproxin Janssen-CilagClarithromycin XL Novartis 2ClobazamClomethiazole Cipramil Klaricid Klaricid SS 1 Not known to be hygroscopic Clomipramine BayerClonazepam Ethanol vaporises out of the capsule when Clopidogrel Heminevrin Frisium Lundbeck AbbottCloral Betaine Abbott Anafranil 1 2 Clozapine Rivotril 4Co-amilofruse AstraZeneca 5/40 May absorb a small amount of water over time; light Co-amilofruse 3 Plavix 2 Sanofi Aventis Welldorm 1 Cephalon UK stable for 6 months Probably - Co-amilofruse 4 from light Protect Co-amilozide 2 Should only be dispensed in glass bottles Clozaril Roche stable for 4 weeks Co-beneldopa Probably Lasoride Alphashow from moisture Protect Co-beneldopa SS - CP 4 - APS 3Co-careldopa Generics (UK) Novartis Madopar Borg 4 Madopar Store in dark 2 2 2 stable for 7 days Probably Sinemet 2 Roche 3 Roche from light Protect BMS 4 5 stable for 14 days Probably Stable for at least 14 days 1 is hygroscopic Powder humidity and congeal with other tablets in the packaging compliance aid hydrochlorothiazide Alendronate 10mg/70mg FosamaxAlfacalcidol MSDAlfuzosin Allopurinol One AlphaAmiloride/ 2 LeoAmiodarone Xatral / XLAmiodarone ZyloricAmisulpride ModureticAmlodipine SS 1 CordaroneAmphotericinAnastrazole - Alpharma GSK BMS Moisture sensitive; can become sticky out of original SolianApomorphine SSAripiprazole Istin 2 Fungilin 2 Aspirin ArimidexAspirin 2 2 UprimaAspirin SS AbilifyAspirin EC 2 BSM PfizerAtenolol AstraZenecaAtenolol Angettes Abbott 4Atenolol/chlortalidone 1 - 2 Atenolol/co-amilozide 50 1 BSM Tenoretic/Tenoret AstraZeneca Nu-Seals Caprin ok for short term storage in a compliance aid Probably Atenolol/nifedipine Hygroscopic Kalten 2 BSM 2 Disintegrates in the presence of small amounts water Atazanavir sulphate TenorminAtorvastatin Tenif - CP Lilly 1 ReyatazAuranofin Pinewood AlpharmaBaclofen AstraZeneca AstraZeneca 1 Hygroscopic Baclofen 1 2 2 1 LipitorBambuterol HCl Hygroscopic BSM 2 2 AstraZenecaBenperidol to be hygroscopic Potential Ridaura Not suitable as sensitive to atmospheric moisture 2 Beta-cardone not suitable as sensitive to moisture Probably Lioresal BambecBetahistine 2 PfizerBetamethasone - APSBetamethasone Betnesol Yamanouchi Benquil SotalolBexarotene AstraZeneca Cephalon UK 2 BetnelanBicalutamide Serc 3 1 2 2 Bisoprolol Celltech HansamBisoprolol Disintegrates in bright sunshine Celltech from moisture Protect Bisoprolol Targretin Celltechtablet CasodexBumetanide 1 2 SolvayBuprenorphine HCl 2 Cardicor 2 Soluble Buprenorphine HCl Zeneus Pharma - APS Temgesic 4 AstraZeneca - 2 Burinex Subutex 2 Merck RB 2 RB Leo 2 IVAX 2 4 2 4 stable for 7 days Probably Generic nameAcarboseAcetazolamide Aciclovir Brand nameAciclovirAciclovir dispersible Diamox / SR Company GlucobayAlendronate 5mg Zovirax dispersible GSK Goldshield Code Zovirax Additional information Fosamax Bayer - Pfizer 2 GSK 1 MSD 4 2 Dispersible tablet Should be stable for 7 days 2 5 Stable for 3 months at 40C and 75% relative The stability of drugs in compliance aids, based on information provided by manufacturers (acarbose to co-careldopa) www.pjonline.com 21 January 2006 The Pharmaceutical Journal (Vol 276) 77 Articles tablets) 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) ethylsuccinate folic acid sodium ascorbate folic acid nortriptyline Motival SS 2 Generic nameErgometrineErythromycinErythromycin BP Brand nameErythromycin - Celltech Company Erymax ErythromidErythromycin stearateEscitalopram Erythocin Code 2 Erythroped AEsomeprazole Additional information AbbottEtidronate disodium Zeneus Pharma Abbott 4 Ethamsylate Abbott Cipralex DidronelEthinylestradiol Nexium 3Etoposide 2 Felodipine from light Protect 2 DicyneneFerrous fumarate/ - Celltech Lundbeck P&G AstraZenecaFerrous sulphate Pregaday 4 Vepesid 5 2 SS Plendil 2 stable for 6 months Probably Stable for 6 months at 25C and relative humidity of 60% - Celltech BMS 2 AstraZeneca 2 2 1 Alpharma Cytotoxic 4 stable for maximum of 14 days (could taint other Probably Ferrous sulphateFerrous sulphate/ FerrogradFerrous sulphate/ Ferrograd CFinasteride Ferrograd folic Abbott Abbott Abbott 2 2 Flucloxacillin ProscarFluconazole 2 FludrocortisoneFluphenazine HCl Floxapen MSDFluphenazine/ Florinef Diflucan ModitenFluoxetineFlupentixol GSK 1Flupentixol Pfizer BMS SSFlurazepam tablets when should not handle crushed or broken Women Flurbiprofen Prozac 2 Flutamide Depixol 4 Fosinopril Fluanxol 2 DalmaneFurosemide 2 Froben/SRFurosemide LillyFurosemide/potassium Lundbeck Drogenil Lundbeck LasikalGabapentin Valeant Abbott StarilGemfibrozil - 4 4Gliclazide 4 - CPGlipizide Schering Plough 2 stable for 4 weeks Probably 2 2 Borg stable for 4 weeks Probably Gliquidone stable for up to 4 weeks Probably Neurontin BMSHaloperidol LopidHydroxycarbamide 2 Alpharma Diamicron/MRHydroxychloroquine Pfizer 3 GlibeneseHydroxyzine Hydrea Glurenorm Servier 2 4 Plaquenil from light Protect - Pfizer stable for 4 weeks Probably 2 Pfizer SS 4 Atarax BMS SS 2 stable for 8 days Probably 2 IVAX 2 1 Pfizer 2 Cytotoxic 4 4 stable for 7 days Probably stable for 7 days Probably will cause levodopa to turn black on prolonged exposure plastic dispensing bottle eg, container, SPC states “must be stored in the original package” moisture; 10% loss of potency occurred when exposed to 40C and 75% humidity for 13 weeks misoprostol aspirinparacetamol and capsules dispensing bottle Generic nameCo-careldopaCo-careldopa Brand name Sinemet CR Company Sinemet 110/250 BMS BMS Code Additional information 1 1 Blue dye can fade on light exposure; also moisture is hygroscopic Powder Co-danthrusateCo-trimoxazoleCodeine phosphate NormaxColchicineCyclizine Septrin - DanazolDantrolene sodium CelltechDemeclocycline - Celltech GSK DantriumDesloratidine ValoidDexamethasone 2 CP LedermycinDexamfetamine sulphate Danol 2 DexedrineDiazoxide P&G Neoclarityn 2 Diclofenac EC/SR/Retard - Voltarol Goldshield AmdipharmDiclofenac and 2 Celltech SS Schering Plough 2 3 4 2 Didanosine chewable EudemineDidanosine EC Novartis 2 Arthrotec Videx Light sensitive to be hygroscopic Unlikely Didronel PMO OrganonDigitoxin 2 2 CelltechDigoxin Videx EC Pfizer 4 BMSDiltiazem hydrochloride - DilzemDiltiazem 2 to be any issues Unlikely Diltiazem BMS 1Diltiazem - 1Diltiazem Tildiem/LA/Retard Lanoxin Misoprostol is extremely moisture sensitive and may degrade Zeneus Pharma SSDipyridamole MR 4 Hygroscopic Slozem P&G 2 Adizem SR/XLDipyridamole MR/ Retard Persantin Angitil SR/XL Celltech GSK Napp BI 2 Dipyridamole Asasantin Retard 1 Merck TrinityDisopyramide BI 2 Docusate sodium See Calcium carbonate and etidronate 4Domperidone Motilium 2 Persantin 2 5Domperidone/ 4 Dioctyl Rythmodan stable for 14 days Probably 5 Moisture sensitive; stable for 30 days out of the original stable for 4 weeks Probably Donepezil SS BIDosulepin tablets Borg Domperamol plastic eg, Stable for 30 days out of the original container, SchwartzDosulepin - ServierDoxazosin 2 Aricept 4 2 Doxazosin 3 4 from light Protect Doxepin ProthiadenEfavirenz Pfizer stable for 8 days Cardura Probably Generics (UK)Enalapril Cardura XL 4 Abbott stable for 7 days Probably 4Ergocalciferol Pfizer Sinequan Pfizer Sustiva 2 stable for 14 days Probably Innovace Pfizer 2 1 - BMS MSD Not recommended for inclusion in compliance aid; 2 2 1 Celltech May hydrolyse at high temperature and in the presence of 2 The stability of drugs in compliance aids, based on information provided by manufacturers (co-careldopa to hydroxyzine)

78 The Pharmaceutical Journal (Vol 276) 21 January 2006 www.pjonline.com Articles quickly; moisture can affect release mechanism gloves if breaking or dividing the tablets due to potential contact dermatitis moisture in the air relative humidity up to 75% with a dessicant and capsules orodispersiblemisoprostol on lidding paper of each tablet pouch tablets and capsules caplet/capsules effervescent tablets Generic nameMetronidazoleMinocyclineMinoxidil Brand nameMirtazapine Flagyl Company Minocin MRMisoprostolModafinil Code Loniten ZispinMorphine sulphate Additional information Wyeth HawgreenMoxifloxacinNadolol Cytotec MST Continus 3Naftidofuryl Pfizer Provigil 4Nalidixic acid Napp Organon Must be protected from light AveloxNaltrexone stable for 7 days* Probably PfizerNaproxen and 1 2 Praxilene Corgard Cephalon UK 2 NegramNevirapine Hygroscopic; as an alternative, can write days of the week 2 BayerNicardipine 1 Nalonex NapratecNicardipine Merck SS Moisture sensitive and may degrade Nicorandil SSNifedipine 4 Viramune Pfizer BMS Cardene 2 Nifedipine Should be stable for 7 days Cardene SR 2 2 Ikorel BI 2 Adalat Retard 2 Yamanouchi Yamanouchi 2 3 Adalat LA Bayer Sanofi Aventis 4 from light. Protect 5 Bayer 1 Stable for at least 7 days in a dry environment light sensitive Very 1 light sensitive and will significantly degrade very Very NifedipineNimodipine NitrazepamNizatidineNorethisterone Coracten SR/XL NimotopNystatin CelltechOlanzapine Mogadon Utovlan Axid Bayer 2 Olanzapine Velotabs Valeant Nystan Zyprexa Zyprexa Velotabs PfizerOlsalazine sodium 4 Lilly Lilly 2 Omeprazole capsules Dipentum Lilly Should be stable for 7 days BMSOmeprazole capsules 2 - Losec 1 4Omeprazole MUPS CelltechOrphenadrine 4 fragile/brittle — may disintegrate due to 1 Particularly stable for up to 4 weeks Probably Oxybutynin Losec MUPS AstraZeneca 2 Oxybutynin stable for up to 4 weeks; sensitive light; wear Probably is hygroscopic Powder Generics (UK)Oxybutynin XL 5 AstraZeneca Disipal 1 5Pancreatin Cystrin Stable for 14 days at room temperature (25–30C) and Hygroscopic Paracetamol Ditropan XL Lyrinel Stable for 3 months at 25C and relative humidity of 60% Paracetamol/codeine Yamanouchi Solpadol 2 Paracetamol/codeine SS Creon Janssen-Cilag SS - 1 - SS in high density polyethylene bottles Hygroscopic; packaged 2 Solvay 2 Alpharma SS 2 2 4 stable for up to 28 days Probably 1 offers a barrier against moisture* /hydrochlorothiazide CoAprovel BMS 2 orodispersible hydrochlorothiazide hydrochlorothiazide acetate acetate Provera Pfizer 2 Generic nameIbuprofenIndapamide Inositol nicotinate Brand nameIrbesartanIrbesartan Company Hexopal Brufen/Retard Natrilix/SRIsoniazid Code AbbottIsosorbide mononitrate Additional information Aprovel Servier SSIsosorbide mononitrate - Isosorbide mononitrate - 2 Cedocard RetardIsosorbide mononitrate 4 Elantan LA - CelltechIsosorbide mononitrate Pfizer BMS ImdurIsosorbide mononitrate 2 stable for 8 days Probably Monomax SR/XLKetoprofen Alpharma 2 SchwartzKetoprofen Trinity IVAX 2 2 MRKetoprofen 4Labetolol hydrochloride 2 AstraZeneca TrandateLamivudine Ketocid stable for up to 14 days Probably 4 5 4Lamotrigine Oruvail OrudisLansoprazole stable for 4 weeks Probably Stable for one month stable for 7 days Probably Celltech Trinity Epivir Lamictal Hawgreen Hawgreen Zoton 2 3 4 3 GSK GSK Must be protected from light stable for 4 weeks Probably Must be protected from light Wyeth 2 2 4 stable for up to 4 weeks in a compliance aid which Probably LansoprazoleLevothyroxineLevothyroxine Zoton FasTabLisinoprilLisinopril - APS WyethLisinopril/ - Lisinopril/ Zestril 1 2 CaraceLithium Carace plus Highly moisture sensitive* Loperamide AlpharmaLopinavir/ritonavir Zestoretic AstraZeneca BMSLosartan BMS 2 Medroxyprogesterone Kaletra 2 Imodium Priadel Farlutal AstraZenecaMedroxyprogesterone 2 2 2 Cozaar AbbottMegestrol Janssen-CilagMemantine HCl SS Pfizer 1MeloxicamMesalazine 2 Moisture sensitive and could change colour MSD EbixaMethionine 2 MegaceMetformin 4Methotrexate MobicMethylphenidate HCl stable for 7 days Probably Asacol 2 Methylphenidate HCl BMS Lundbeck - Celltech RitalinMethylphenidate HCl Glucophage Concerta XL MaxtrexMetolazone BI Equasym 2 Metoprolol tartrate 2 P&G 2 Merck Janssen-Cilag Cephalon UK 1 Betaloc SA Pfizer Celltech 2 Metenix 5 4 1 with a desiccant Packaged 2 AstraZeneca 2 coating is moisture and light sensitive 1 Tablet Borg 2 Cytotoxic 3 from light Protect The stability of drugs in compliance aids, based on information provided by manufacturers (ibuprofen to paracetamol/codeine) www.pjonline.com 21 January 2006 The Pharmaceutical Journal (Vol 276) 79 Articles from packaging tan) furosemide bendroflumethiazide di-citratobismuthate crushable tablets Generic nameSibutramineSimvastatinSotalol Brand nameSotalol ReductilSpironolactone Company ZocorSpironolactoneSpironolactone/Pfizer Code Additional information - Beta-cardone AbbottStavudine - Sotacor LasilactoneSulfasalazine Salazopyrin/EN/EC MSD Celltech 2 Sulpiride 2 Sulpiride BorgTacrolimus BMS 2 IVAX Zerit 2 Tamoxifen AlpharmaTamoxifen DolmatilTamoxifen 3 2 2 SulpitilTamsulosin 3 Prograf with uracilTegafur from light Protect BMS Nolvadex from light Protect Terazosin SS - APSTerbinafine Uftoral - Pfizer sulphate FujisawaTerbutaline Flomax SR 2 AstraZenecaTestosterone Bricanyl 3 2 5 2 Hytrin Yamanouchi BMSTetrabenazine 2 LamisilTheophylline Known to be light labile Stable for 3 months at 30C and 75% humidity 2 Restandol Generics (UK)Theophylline AstraZeneca 3Theophylline Xenazine 25 1 2 Abbott NovartisTheophylline/ephedrine Sensitive to light Organon Slo-Phyllin Franol/PlusThioridazine Cytotoxic Uniphyllin CambridgeThiamine 2 Nuelin SA 2 Tiagabine 1 SS Merck 2 Tiludronic acid NappXLPfizer MellerilTimolol maleate sensitive to moisture and becomes “sticky” Very if removed 3MTimolol maleate/ Benerva 2 Skelid Gabitril 2 BetimTizanidine HCl 2 Prestim Novartis Detrusitol/ Tolterodine 2 Topiramate Roche 2 Tramadol 2 Zanaflex SS Cephalon UK Valeant Trandolapril Valeant 2 acidTranexamic 4 Trazodone Topamax 2 Zeneus Pharma 2 Trimipramine 4 2 Zydol Cyklokapron GoptenTri-potassium Janssen-CilagValdecoxib Pfizer Molipaxin 1 Surmontil sodium EC/Valproate De-Noltab Abbott Pfizer Epilim Hygroscopic; hydroxylates and becomes unstable with water sodium chronoValproate Epilim chrono 2 Sanofi Aventis Sanofi Aventis acidValproic Bextra Yamanouchi 2 2 2 Valsartan 2 SS 2 SS Depakote Pfizer 1 Diovan 1 SS Hygroscopic 2 Hygroscopic Novartis 2 2 (notably the 50µg strength) aid for 14 days storage humidity the dark Can absorb moisture eckitt Benckiser 2 eckitt Benckiser 1 metoclopramide maleate and capsules Generic nameParacetamol/Paroxetine Brand namePenicillamine ParamaxPergolide Company Seroxat Code Distamine SS Additional information Celance Lilly GSK 2 Lilly 2 2 1 Unstable — light sensitive and extremely hygroscopic PerindoprilPerindopril/indapamide Coversyl PlusPhenytoin Epanutin/InfatabPiroxicam Pfizer Servier dispersiblePiroxicam Coversyl chloridePotassium Feldene Melt 2 4 Slow KPravastatin Feldene Pfizer ServierPrazosin stable for 8 days Probably Prednisolone ECPrednisolone 4 Alliance 1Prochlorperazine Lipostat Pfizer stable for 8 days Probably Deltacortril Moisture sensitive Hypovase - APSPropafenone 4 Buccastem HClPropranolol 2 BMSPropylthiouracil May absorb water; probably stable in an airtight compliance Pfizer PfizerPyridostigmine R 2 Arythmol Inderal/Half InderalQuetiapine AstraZenecaQuinapril - Celltech 2 2 2 Quinidine bisulphate Mestinon 2 Quinine sulphate Abbott Kinidin 2 Rabeprazole SeroquelRaloxifene Valeant Accupro - tabletsRamipril 2 AstraZeneca AstraZeneca ParietRanitidine 1 Tritace 2 Ranitidine 4 Pfizer EvistaReboxetine Store in a brown bottle with desiccant Alpharma stable for up to 7 days Probably Ribavirin Janssen-CilagRisedronate sodium 2 - Sanofi AventisRisperidone 1 4 Zantac Lilly 2 Actonel Edronax Hygroscopic stable for up to 7 days Probably Ritonavir RebetolRopinirole Risperdal 2 GSK P&G Generics (UK) PfizerRosuvastatin 1Salbutamol Schering Plough Norvir 2 Salbutamol Janssen-Cilag Requip Hygroscopic and may turn brown 2 Saquinavir 1 2 2 CrestorSaquinavir Hygroscopic and degrades in the presence of water Not known to be hygroscopic or need a drying agent during Volmax AbbottSelegiline HCl SR Ventmax GSKSenna (sennosides) Invirase AstraZeneca Fortovase Senokot Trinity 2 A&H/(GSK) 2 Zelapar 5 1 by patient not required if used within 30 days Refrigeration Roche Roche 4 Stable for up to 28 days below 25C and at 60% relative R Hygroscopic Zeneus Pharma stable for 4 weeks Probably 1 3 3 Hygroscopic Store in the dark stable for 3 months out of the refrigerato; store in Probably SertindoleSertraline Serdolect Lustral Lundbeck Pfizer 3 light sensitive Very 4 The stability of drugs in compliance aids, based on information provided by manufacturers (paracetamol/metoclopramide to valsar

80 The Pharmaceutical Journal (Vol 276) 21 January 2006 www.pjonline.com Articles

Advertisement authorisation urers any information aid. (Refer to SPC for additional stability information.) aid. (Refer light-sensitive. for concern is stated, eg, Individual pharmacists must accept aid. Reason responsibility for putting in a compliance aid. Risks can be minimised by additional use of a black bag. safeguards, eg, compliance aid. Key to stability codes 1. Do not put into a compliance aid. 2. No stability data available, therefore company does not recommend putting in a compliance 3. No stability data available, therefore company does not recommend putting in a compliance 4. No stability data available, but it is probably suitable to put in a compliance aid. 5. but not necessarily in a Stability data available in an alternative container, 6. Stability data available which state that it is suitable to put in a compliance aid. KEY TO Merck Sharp & Dohme; BI, Boehringer Ingelheim; BSM, Bristol-Myers Squibb; GSK, MANUFACTURERS: GlaxoSmithKline; MSD, & Procter P&G, Sanofi Synthelabo Gamble; SS, t and that storage of products in any other way is entirely at the pharmacist’s own risk. information provided in this article has been provided by the marketing authorisation holders for these products. The marketing information provided in this article has been by the marketing om the original packs to compliance aids as it may be outside terms of their product licences. For majority manufact Half Securon SR trandolapril they provide is based on anecdotal evidence or in-house studies as no formal would have been carried out. *The product holders only recommend that their products are stored in accordance with the summary of product characteristics for each produc DISCLAIMERS: It is important to note that the individual manufacturers do not endorse practice of transferring medicines fr Verapamil HCl/Verapamil WarfarinZafirlukast TarkaZaleplonZidovudineZidovudine/lamivudine CombivirZolmitriptan - Goldshield Accolate AbbottZolpidem SonataZopiclone 2 RetrovirZopiclone GSK 2 AstraZeneca ZomigZuclopenthixol 5 Stilnoct Wyeth GSK Zimovane 2 Stable for 30 days at 60-80% relative humidity Clopixol - AstraZeneca 2 SS 2 2 Sanofi Aventis 2 * Lundbeck IVAX 4 2 2mg stable for 14 days; other strengths 4 weeks 3 from light Protect Generic name Vancomycin VardenafilVenlafaxine Brand name XLVenlafaxine Matrigel Vancocin HClVerapamil Company Lilly HClVerapamil Levitra Efexor Efexor XL Code Additional information Univer Securon/SR/ 4 Bayer Wyeth Wyeth stable for up to 4 weeks Probably Abbott Zeneus Pharma 4 4 4 1 2 Should be stable for 7 days stable for 7 days* Probably Moisture sensitive* The stability of drugs in compliance aids, based on information provided by manufacturers (vancomycin to zuclopenthixol) www.pjonline.com 21 January 2006 The Pharmaceutical Journal (Vol 276) 81