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Vol. 19. Issue 75.
Pages 50-63 (April - June 2017)
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Vol. 19. Issue 75.
Pages 50-63 (April - June 2017)
Original article
DOI: 10.1016/j.rmu.2017.03.001
Open Access
Medications that should not be crushed
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S.L. Gracia-Vásquez
Corresponding author
sandra.graciavs@uanl.edu.mx

Corresponding author at: Universidad Autonoma de Nuevo Leon, UANL, Facultad de Ciencias Químicas, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, Nuevo León CP 66455, México. Tel.: +52 8329 4000.
, P. González-Barranco, I.A. Camacho-Mora, O. González-Santiago, S.A. Vázquez-Rodríguez
Universidad Autonoma de Nuevo Leon, UANL, Facultad de Ciencias Químicas, San Nicolás de los Garza, Nuevo León, México
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Statistics
Figures (1)
Tables (3)
Table 1. Demographics of the population.
Table 2. Reasons not to split medications.
Table 3. Oral medications that should not be splitor crushed.
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Abstract
Goal

To evaluate the knowledge about medications that could or could not be crushed or split among a group of patients in the Monterrey metropolitan area, and make a list of medications available in México that should not be crushed or split.

Material and methods

A descriptive, observational, transverse study was conducted using validated surveys among 950 patients undergoing medical treatment that went to clinics in the cities of San Nicolás de los Garza, Monterrey and Guadalupe of the Monterrey metropolitan area. The survey included a series of questions aimed at learning the patients’ level of knowledge regarding which drugs can be split or crushed. In order to collect the list of medications, several databases were consulted.

Results

Of the study group, 80.3% had crushed or split a tablet prior to its administration, most of them to facilitate oral intake. Fifty four percent (54.4%) did not ask their physicians about this procedure. Seventy two (72.5%) percent considered that not all tablets should be crushed, but they did not know the exact reason why. An extensive list of medications available on the Mexican market that should not be crushed or split was presented.

Conclusions

There is an urgent need to improve the information available regarding what dosage forms can be split or crushed in order to prevent medication errors.

Keywords:
Dosage forms
Tablets
Enteric-coated
Effectiveness
Administration and dosage
Full Text
Introduction

According to the World Health Organization (WHO), health is defined not only as the absence of disease, but also as a state of physical, psychological and social well-being as an individual, as well as collectively. Thus, the concept of public health acknowledges the fact that health worker interventions include not only clinical services, which focus mostly on somatic and psychological aspects, but also social interventions such as production, rent distribution, consumption, housing, work, environment, etc.1

On the other hand, the irrational use of medications is also a public health concern and a major problem worldwide. This problem has been detected, and international organizations such as the WHO have developed different projects and guidelines to reduce it.2 Rational use of medications require that the patients receive the correct medications, each according to their clinical needs, as well as the correct dose and for the proper period of time, all this at the lowest possible cost for the patients and their communities.3 Public education on this subject is fundamental, since the vast majority of medications are prescribed by a physician, including dosage, frequency, length of treatment and the correct method of administration; and even if a pharmacist were able to solve all the patient's questions on common administration practices and the best hours to take the medications, it is the patient who decides whether or not to follow those instructions, basing his/her decision on a complex set of family beliefs, social, economic and health factors. The patient decides whether or not to buy the medication, take the right doses at the correct frequency, and take it as indicated or split it, especially when dealing with over-the-counter medications. Being well-informed is considered a right for the patient, but it is also an obligation for them to actively participate in the care of their well-being in conjunction with health care professionals.3,4

As a part of a pharmaceutical treatment, splitting (cutting in half) or crushing medications has been an accepted practice as a way of obtaining the prescribed dose when a specific dose is not available. For example, in pediatric or geriatric patients for whom, more often than not, the proper doses are not available on the market. Other examples include cases where there is a need to provide proper fractioned doses within a flexible regimen, when there is a need to reduce or increase the dosage in a dosing regimen, when there is a need to begin therapy with the lowest possible dose in order to avoid an incidence of adverse effects, when there is a need to adjust the therapeutic response of an individual patient, as an aid in the administration of large tablets which patients find hard to swallow whole, and as a way of saving using cheaper larger dose medications in the required proportions.5–14

However, there are pharmaceutical dosage forms which, in principle, should never be crushed. Amongst these are those that come with an enteric coating used for drugs which are inactivated by gastric acid, or that could irritate gastric mucous and used for delayed release. Other dosage forms which should never be crushed are those for sublingual administration, these are designed so that the drug dissolves quickly for a better absorption, thus reaching the bloodstream in a shorter period of time. Certain tablets with a polymeric or sugar coating which disguise unpleasant flavors and smells that avoid mucous irritation or protect active ingredients which are affected by light or humidity should also not be crushed or split, as well as effervescent or dispersible pharmaceutical dosage forms which are designed to dissolve or disperse in water before ingestion; if these are chewed, they could lose their ability to dissolve quickly, thus possibly causing a loss of dosage, in addition to presenting effervescence in the mouth if it is not dissolved in water first. Soft gelatin capsules (with liquid content) should also not be chewed or split, since the extraction of the liquid inside may lead to an incorrect dosage. In the case of medications with prolonged or extended released, if the developed system which contains the dose is destroyed, incidence of collateral side effects or the toxicity of the medication may increase when releasing a greater dose of the active ingredient.15–18 Other formulations which may present problems when crushed are medications with carcinogenic potential, not because their pharmacokinetic characteristics are modified, but because of the risk that tampering with it involves. Some active ingredients like warfarin or levothyroxine have small therapeutic windows; that is to say, if split in uneven parts and ingested, elevated doses of the medication are obtained for immediate absorption and can potentially cause toxicity, or result in a dosage which is under the therapeutic dose.5,19–23

The objective of this study was to evaluate the knowledge of a group of patients in Monterrey, Nuevo León, México and its metropolitan area has about oral medications that should not be split or crushed, and to gather commercial names of medications on the Mexican market which should not be altered.

Material and methods

An observational, transversal, descriptive study was conducted through a previously validated survey. The surveys were applied to those patients who were on medical treatment at that moment and visited clinics and hospitals located in Monterrey, San Nicolas and Guadalupe, both cities located in the metropolitan area of Monterrey, Nuevo Leon, México. Pharmacists were in charge of conducting the survey, and the surveys were applied between July and December of 2015. All patients provided a signed consent prior to the application of the instrument. In the case of minors, their guardians provided said consent. The survey included a series of questions aimed at understanding the degree of knowledge patients had about which medications could be split and/or crushed.

The instrument was developed by experts in the area after a thorough bibliographic review. The items were then evaluated by an expert panel in the field of assistential pharmacy with a doctoral degree in Pharmacy, and finally, these evaluated questions were first applied to a small population group that was given a close follow-up to see if they fully understood each of the questions and once any situations found were corrected, a survey was applied to a pilot group close to the target population of our survey (30 patients), i.e. patients in the metropolitan area of Monterrey. Once this was done, the validated survey was applied to the population described. The responses to the survey were stored in a database and processed in Excel. Descriptive statistical analysis was performed. For the compilation of the list of medicines that should not be splitted or crushed, consultations were carried out from various sources of up-to-date information, such as scientific articles of indexed journals, as well as secondary bibliographic sources, specifically PubMed, EBSCO, and LexiComp, and tertiary sources such as books of pharmaceutical technology and dictionaries of pharmaceutical specialties, among others.

Results

The study involved 950 people from different communities in the metropolitan area of Monterrey, N.L., México; their demographic characteristics are shown in Table 1.

Table 1.

Demographics of the population.

Characteristic  Frequency (%) 
Gender
Male  444 (46.7) 
Female  506 (53.3) 
Age range
10–29  431 (45.4) 
30–49  383 (40.3) 
50–69  127 (13.4) 
70–89  9 (0.9) 
Average  32.0 
Average±SD  33.8±13.6 
Schooling level
None  12 (1.3) 
Elementary  88 (9.3) 
Junior high  257 (27.0) 
High school  427 (45.0) 
Bachelor's  137 (14.4) 
Postgraduate  29 (3.0) 
Employment status
Working  746 (78.5) 
Not working  204 (21.5) 

N=950; SD, standard deviation.

Results showed that 80.3% reported having split or crushed a tablet prior to administration, the main reason (49.8%) being to facilitate administration and swallowing, followed by an indication by the physician (20.0%), to adjust the dose (22.0%), to disguise a bad taste (7.2%), and 1.0% of the respondents mentioned another reason. The most frequently used instrument (50%) for splitting the tablets was a knife, followed by the hands (29%), the teeth (11%), and finally a splitter (10%) (Fig. 1).

Figure 1.

Instruments most commonly used to split tablets.

(0.05MB).

Most respondents (72.5%) considered that not all medicines can be splitted or crushed, and when questioned about why, the most common response was the fact that it could cause the drug to have no effect (40.0%); other reasons are shown in Table 2.

Table 2.

Reasons not to split medications.

Motive  Frequency (%) 
Loss of drug effect  380 (40.0) 
Bad taste  209 (22.0) 
Irritation of the stomach  190 (20.0) 
Extended or prolonged released medications  68 (7.2) 
Possibility of toxicity  19 (2.0) 
Other reasons  84 (8.8) 

n=950.

Further results show that 54.4% did not consult a physician before carrying out this practice. A large part of the respondents, 895 people (94.2%), were interested in knowing more about medications that could or could not be split in two or crushed, and would like to receive this information from a health professional.

Moreover, 49% of the respondents reported having had some discomfort when ingesting a split tablet, the most frequent being stomach irritation. Forty nine percent (49.6%) said that the main consequence of crushing tablets is the bitter taste that may occur and some less common ones would be: oral mucosal irritation, toxicity, dose inaccuracy and dental staining.

Table 3 lists orally administered medications that should not be crushed or splitted, thereby avoiding side effects, toxicity or inefficacy caused by this practice. Although the list is numerous and serves as a guide for health professionals in México, there are other medicines on the market that are not listed.19,24–26

Table 3.

Oral medications that should not be splitor crushed.

Commercial name  Generic name  Pharmaceutical dosage form  Reasons or comments 
ABBATIN  Montelukast sodium  Tablets  Coated 
ACORTRAL  Sertraline hydrochloride  Tablets  Coated 
ACXION AP  Phentermine hydrochloride  Tablets  Prolonged release 
ADALAT OROS  Nifedipino  Tablets  Prolonged release 
AFINITOR  Everolimus  Tablets  Do not chew or crush
By manufacturer 
AGIOLAX  Plantago ovata
Senna angustifolia 
Granules  Coated 
AGRIXAL  Omeprazole  Capsules  Enteric coatingc 
AKINETON DELAYED  Biperidene hydrochloride  Tablets  Prolonged release 
AMARLY XM  Glimepiride
Metformin hydrochloride 
Tablets  Prolonged release 
ANGELIQ  Estradiol
Drospirenone 
Tablets  Coated 
ANGIOTROFIN DELAYED  Diltiazem hydrochloride  Tablets  Prolonged release 
ANTAGIN  Indomethacin  Capsules  Prolonged release 
ARCALION  Sulbutylamine  Tablets  Coated 
ARCOXIA  Etoricoxib  Tablets  Coated 
ASA 100  Acetylsalicylic acid  Tablets  Prolonged released 
ASACOL  Mesalazine  Tablets  Delayed release 
ASOFLON  Tamsulosin  Capsules  Controlled release 
ASPIRIN PROTECT  Acetylsalicylic acid  Tablets  Enteric coatingc 
ATEMPERATOR  Magnesium valproate  Tablets  Enteric coatingc 
ATEMPERATOR LP  Magnesium valproate  Tablets  Prolonged release 
ATHOS  Dextromethorphan hydrobromide  Capsules  Prolonged release 
ATRIPLA  Efavirenz
Emtricitabine
Tenofovirdisoproxilfumarate 
Tablets  Coated 
AVADEN  Estradiol
Gestodeno 
Tablets  Prolonged release 
AVODART  Dutasteride  Capsules  Liquid fillingk 
BEDOYECTA  Vitamins: C, B1, B2, B6, B12 Folic acid  Capsules  Liquid fillinge 
BENEDORM  Melatonin  Tablets  Sublingualh 
BIOMESIN
COMPOUND 
Hyoscine butylbromide
Metamizole sodium monohydrate 
Tablets  Coated 
BI-PROFENID  Ketoprofen  Tablets  Prolonged releaseg 
BOREALIS  Finasteride  Tablets  Coated 
BROSPINA SL  Buprenorphine hydrochloride  Tablets  Sublingualh 
BRUNACOL  Ketorolac tromethamine  Tablets  Coated 
BUSCAPINA COMPOSITUM  Butylhioscinbromide
Sodium metamizole monohydrate 
Tablets  Coated 
CAPRELSA  Vandetanib  Tablets  Coated 
CASDROGEN  Bicalutamide  Tablets  Do not chew
By manufacturer 
CECLOR 12 H  Cefaclormonohydrate  Tablets  Prolonged releaseg 
CECLORDOX  Cefaclor
Bromhexine hydrochloride 
Tablets  Prolonged releaseg 
CEFABIOT  Cefuroxime axethyl  Tablets  Coated 
CEFURACET  Axetilcefuroxime  Tablets  Coated 
CEPACAÍNA  Cetylpyridinium chloride
Benzocaine 
Lozenge  Do not chew
Local action 
CEPACOL  Cetylpyridinium chloride  Lozenge  Do not chew
Local action 
CERTICAN  Everolimus  Tablets  Do not break
By manufacturer 
CERVILAN  Lomifilina
Dihydroergocristinemesylate 
Coated Tablets  Coatedc 
CIALIS  Tadalafil  Tablets  Coated 
CIPROFLOX DM  Ciprofloxacin hydrochloride hydrochloride  Tablets  Prolonged release 
CIPROXINA  Ciprofloxacin hydrochloride monohydrate  Tablets  Do not break
By manufacturer 
CIPRO XR  Ciprofloxacin hydrochloride  Tablets  Prolonged release 
CITOX  Citalopram hydrobromide  Tablets  Coated 
CLARITYNE D  Loratadine
Phenylephrine hydrochloride 
Tablets  Sustained release 
COMBODART  Dutasteride
Tamsulosin hydrochloride 
Capsules  Mucosal irritation 
CONCOR  Bisoprolol fumarate  Coated tablets  Coated 
CONTROLIP  Fenofibrate  Capsules  Swallow whole
By manufacturer 
CORPOTASIN CL  Potassium bicarbonate
Potassium chloride
Lysine hydrochloride 
Tablets  Effervescentf 
CORPOTASIN LP  Potassium chloride  Tablets  Prolonged release 
CREON  Pancreatin  Capsules  Microspheres with enteric coatingc 
CRIAM PROLONGED RELEASE  Magnesium valproate  Tablets  Prolonged releaseg 
CRONOCAPS  Melatonin  Capsules  Prolonged release 
CYMBALTA  Duloxetine hydrochloride  Capsules  Delayed release 
DABEX XR  Metformin hydrochloride  Tablets  Prolonged release 
DAGLA  Itopride hydrochloride  Tablets  Coated 
DANZEN  Serratiopeptidase  Tablets  Enteric coatingc 
DAXON  Nitazoxanide  Tablets  Dispersablei 
DAXXAS  Roflumilast  Tablets  Coated 
DEBEONE DT NF  Metformin hydrochloride  Tablets  Prolonged release 
DEPAKENE  Valproic acid  Capsules  Mucosal irritation 
DEXIDEX  Nitazoxanide  Tablets  Coated 
DEXIVANT  Dexlansoprazole  Capsules  Delayed release 
DIAMICRON MR  Glycazide  Tablets  Prolonged release 
DIANE  Cyproterone
Ethinylestradiol 
Coated tablets  Coated 
DICETEL  Pinaverium bromide  Tablets  Coated 
DILACORAN DELAYED  Verapamil  Tablets  Prolonged release 
DIMEFOR-G  Metformin hydrochloride
Glibenclamide 
Tablets  Coatedb 
DIMEGAN-D  Loratadine
Phenylephrine hydrochloride 
Capsules  Prolonged release 
DINORAX  Metformin hydrochloride  Tablets  Coated 
DINORAX C  Metformin hydrochloride
Glibenclamide 
Tablets  Coated 
DIURMESSEL  Furosemide  Tablets  Do not break
By manufacturer 
DOLAC 30  Ketorolac tromethamine  Tablets  Sublingual 
DOLFLAM-RETARD  Diclofenac sodium  Coated tablets  Prolonged release 
DOLOCAM  Meloxicam  Tablets  Sublingualh 
DORIXINA RELAX  Lysine clonixinate
Cyclobenzaprine hydrochloride 
Tablets  Coated 
DOYCUR  Clarithromycin  Tablets  Coated 
DUCICLON  Diclofenac sodium
Vitamins: B1, B6, B12 
Coated tablets  Coated 
DUPLAT  Pentoxifylline  Coated tablets  Coated 
DUSPATALIN  Mebeverina  Capsules  Prolonged release 
EBIXA  Memantine hydrochloride  Tablets  Do not break
By manufacturer 
EFFIENT  Prasugrel  Tablets  Coateda 
EMSELEX  Darifenacine bromide  Tablets  Prolonged release 
ENDOCODIL XR  Oxycodone hydrochloride  Tablets  Prolonged release 
ENTOCORT  Budesonide  Capsules  Prolonged release 
EPIVAL  Valproate semisodium  Tablets  Enteric coatingc 
EPIVAL ER  Valproate semisodium  Tablets  Prolonged release 
EPRATENZ DOX  Eprosartan
hydrochlorothiazide 
Tablets  Coated 
ESBELCAPS  Fenproporex hydrochloride Diazepam  Capsules  Prolonged release 
ESCAPIN-N  Butylphoscinebromide Paracetamol  Coated tablets  Coated 
ESPAVEN ENZIMÁTICO  Pancreatin
Ox bile extract
Dimethicone
Cellulase 
Coated tablets  Enteric coatingc 
EVADOL  Diclofenac sodium  Coated Tablets  Coatedc 
FEPROREX  Fenproporex hydrochloride  Capsules  Prolonged release 
FERROTEMP  Ferrous fumarate
Thiamine mononitrate 
Capsules  Prolonged release 
FLONORM  Rifaximin  Coated Tablets (Dragee)  Coated 
FLOXACIN  Norfloxacin  Tablets  Coated 
FORCEDOL  Tramadol hydrochloride
Ketorolac tromethamine 
Tablets  Sublingual 
FOSAMAX PLUS  Alendronate sodium
Colecalciferol 
Tablets  Mucosal irritation 
FOSFONAT  Ibandronic acid  Tablets  Mucosal irritation 
FOTORAL  Vitamins and minerals  Capsules  Liquid fillinge 
FRAVITAN  Vitamins and minerals  Capsules  Liquid filling 
GALEDOL  Diclofenac sodium  Coated Tablets  Prolonged release 
GALEDOR  Diclofenac sodium  Tablets  Effervescentef 
GIMACLAV  Amoxicillin potassium clavulanate  Tablets  Coated 
GLIMETAL LEX  Glimepiride
Metformin hydrochloride 
Tablets  Prolonged release 
GLUPROPAN  Glimepiride  Tablets  Produces unpleasant taste 
HYZAAR  Losartan potassium
Hydrochlorothiazide 
Tablets  Coatedg 
ILIMIT  Drospirenone
Ethinylestradiol 
Tablets  Coated 
IMDUR  Isosorbide mononitrate  Tablets  Prolonged release 
IMPAZA  Endothelial anti-NO-synthase polyclonal antibody  Tablets  Orodispersable 
IRESSA  Gefitinib  Tablets  Sublingualh 
ISENTRESS  Potassium raltegravir  Tablets  Coatedb 
ISMIGEN  Freeze-dried bacterial lysate  Tablets  Sublingualh 
ISORBID  Isosorbide dinitrate  Tablets  Sublingualh 
ISORBID A.P  Isosorbide dinitrate  Capsules  Prolonged release 
ITALNIK  Ciprofloxacin hydrochloride  Tablets  Prolonged release 
ITRAVIL AP  Clobenzorex hydrochloride  Tablets  Prolonged release 
JUMSLIM  Tamsulosin hydrochloride  Capsules  Prolonged release 
KALETRA  Lopinavir
Ritonavir 
Tablets  Coated 
KALIOLITE  Potassium chloride  Coated tablets  Coatedc 
KEPPRA XR  Levetiracetam  Tablets  Prolonged release 
KIVEXA  Abacavir sulfate
Lamivudine 
Tablets  Coated 
KLARICID O.D.  Clarithromycin  Tablets  Prolonged release 
KOMBIGLYZE XR  Saxagliptin
Metformin hydrochloride 
Tablets  Prolonged release 
KYTRIL  Granisetron hydrochloride  Coated tablets  Coated 
LACDOL-S  Ketorolac tromethamine  Tablets  Sublingualh 
LEFLOXIN  Levofloxacin hemihydrate  Tablets  Coated 
LEGALON  Silymarin  Coated tablets  Coated 
LODESTAR  Losartan potassium  Tablets  Coated 
LODESTAR ZID  Losartan potassium
Hydrochlorothiazide 
Tablets  Coated 
LOGIMAX  Felodipino
Meproprololsuccinate 
Tablets  Prolonged release 
LOSECA  Omeprazole  Capsules  Prolonged release 
LUVOX  Fluvoxamine maleate  Tablets  Coated 
LYSOMUCIL  Acetylcysteine  Tablets  Effervescentf 
MACRODANTINA  Nitrofurantoin  Capsules  Prolonged release 
MAVIGLIN  Metformin hydrochloride
Glibenclamide 
Coated tablets  Coated 
MAZDA  Venlafaxine hydrochloride  Capsules  Prolonged release 
MESTINON TIMESPAN  Pyridostigmine bromide  Tablets  Prolonged release 
MICARDIS  Telmisartan  Tablets  Prolonged release 
MICROGYNON CD  Levonorgestrel
Ethinylestradiol 
Coated tablets  Coated 
MICROLUT  Levonorgestrel  Coated tablets  Coated 
MICROMYCIN  Minocycline hydrochloride  Capsules  Controlled released 
MICTASOL  Norfloxacin
Phenazopyridine chlorhydrate 
Tablets  Do not break
By manufacturer 
MONOCRAT DEPOT  Isosorbide mononitrate  Tablets  Prolonged release 
NATRILIX SR  Indapamide  Tablets  Prolonged release 
NEDICLON  Diclofenac sodium  Coated tablets  Prolonged release 
NEOBES  Amfepramone hydrochloride  Capsules  Prolonged release 
NEOGYNON  Levonorgestrel
Ethinylestradiol 
Coated tablets  Coated 
NEO-MELUBRINA  Sodium metamizole  Tablets  Effervescent 
NEPTALIP EXTENDED  Bezafibrate  Tablets  Prolonged release 
NEUGERON LP  Carbamazepine  Tablets  Prolonged release 
NEUPAX  Alprazolam
Sulpiride 
Tablets  Sublingualh 
NEXIUM-MUPS  Esomeprazole magnesium trihydrate  Tablets  Coatedj 
NIFEZZARD  Nifedipino  Capsules  Liquid fillinge 
NORVIR  Ritonavir  Tablets  Mucosal irritation 
OBECLOX LP  Clobenzorex  Tablets  Prolonged release 
OGASTRO  Lansoprazole  Capsules  Coatedj 
OMACOR  Ethyl esters of omega-3 fatty acids  Capsules  Liquid fillinge 
ONEMER  Ketorolac tromethamine  Tablets  Coated 
ONEMER SL  Ketorolac tromethamine  Tablets  Sublingualh 
ONOTON  Pancreatin
Hemicellulase
Simethicone 
Tablets  Enteric coatingc 
OPORTUNA  Levonorgestrel  Coated tablets  Coateda 
OSSOPAN  Calcium
Phosphorus
Protein 
Coated tablets  Coateda 
PALATRIN  Lansoprazol  Tablets  Enteric coatingc 
PALEXIA DELAYED  Tapentadol hydrochloride  Tablets  Prolonged release 
PANKREOFLAT  Pancreatin
Dimethicone 
Tablets  Enteric coatingc 
PANTOZOL  Pantoprazole sodium sesquihydrate  Granules  Coatedj 
PARAMIX  Nitazoxanide  Coated tablets  Coateda 
PARAMIX  Nitazoxanide  Tablets  Dispersablei 
PAXIL  Paroxetine hydrochloride  Tablets  Do not break
By manufacturer 
PAXIL CR  Paroxetine hydrochloride  Tablets  Prolonged release 
PENTASA  Mesalazine  Tablets  Prolonged release 
PENTASA  Mesalazine  Granules  Prolonged released 
PHENODICAL  Felodipino  Tablets  Prolonged release 
PHLOGENZYM  Bromelain
Trypsin
Routine 
Coated tablets  Coatedc 
PLANTIVAL  Valeriana officinalis
Melissa officinalis 
Coated tablets  Coateda 
PLASIL ENZYMATIC  Metoclopramide
Bromelain
Dimethicone
Pancreatin
Sodium dehydrocholate 
Coated tablets  Coateda 
PLENACOR LP  Atenolol
Nifedipino 
Capsules  Prolonged release 
PLENDIL  Felodipino  Tablets  Prolonged release 
POSIPEN  Dicloxacillin sodium  Tablets  Prolonged release 
PREDIAL PLUS  Metformin hydrochloride  Tablets  Prolonged release 
PREDXAL PLUS  Telmisartan
Hydrochlorothiazide 
Tablets  Do not break
By manufacturer 
PRENATEX  Vitamins
Minerals 
Coated tabletss  Coated 
PRETERAX  Perindopril arginine Indapamide  Tablets  Coated 
PRILIGY  Dapoxetine hydrochloride  Tablets  Coated 
PRIMOGYN  Estradiol valerate  Coated tablets  Coated 
PROBITOR  Anastrozole  Tablets  Coatedb 
PROCORALAN  Ivabradine hydrochloride  Tablets  Coatedb 
PROGRAF XL  Tacrolimus monohydrate  Capsules  Prolonged release 
PRONTOFORT  Tramadol hydrochloride  Capsules  Prolonged release 
PROPESHIA  Finasteride  Coated tablets  Coateda 
PROTALGINE  Lamotrigine  Tablets  Dispersablei 
PROVAY  Ciprofloxacin hydrochloride monohydrate  Tablets  Coated 
PROZAC 20 DISPERSABLE  Fluoxetine hydrochloride  Tablets  Dispersablei 
PULSARAT  Simvastatin  Tablets  Coatedb 
PYLOPAC  Lansoprazole
Clarithromycin
Amoxicillin 
Tablets  Coated 
QUEDOX  Clarithromycin  Tablets  Coated 
RANTUDIL DELAYED  Acemetacin  Capsules  Coatedj 
RAPIX  Ketorolac tromethamine  Tablets  Sublingualh 
RAYPID  Gemfibrozil  Tablets  Coatedb 
REDOTEX  D-norpseudoephedrine hydrochloride
Triiodothyronine sodium
Atropine sulfate
Aloin
Diazepam 
Capsules  Prolonged release 
REDOTEX NF  D-norpseudoephedrine hydrochloride
Atropine sulfate
Aloin 
Capsules  Prolonged release 
RENAGEL  Sevelamer hydrochloride  Tablets  Coatedb 
RESOTRANS  Prucalopride succinate  Tablets  Coated 
REVLIMID  Lenalidomide  Capsules  Should not be opened or chewed
By manufacturer 
RIFAPRIM  Rifampicin
Trimethoprim 
Coated tablets  Coated 
RIFATER  Rifampicin
Isoniazid
Pyrazinamide 
Coated tablets  Coateda 
RIXTAL  Itraconazole  Capsules  Should be swallowed, do not open
By manufacturer 
SALOFALK  Mesalazine  Tablets  Enteric coatingc 
SAMYR  1,4 Butane adenosine disulfonate  Tablets  Do not break
By manufacturer 
SECOTEX  Tamsulosin hydrochloride  Capsules  Prolonged release 
SECOTEX OCAS  Tamsulosin hydrochloride  Tablets  Prolonged release 
SELOKEN ZOK  Meproprololsuccinate  Coated tablets  Coatedd 
SELOPRES ZOK  Meproprololsuccinate Hydrochlorothiazide  Tablets  Coatedd 
SENOVITAL  Montelukastsodium  Tablets  Coated 
SENSIBIT  Loratadine  Tablets  Orodispersablen 
SERITRAL  Itraconazole  Capsules  Should be swallowed, do not open
By manufacturer 
SERONEX LP  Domperidona  Tablets  Prolonged release 
SEROQUEL XR  Quetiapine  Tablets  Prolonged release 
SERVAMOX CLV  Amoxicillin trihydrate
Potassium clavulanate 
Tablets  Coated 
SIFROL ER  Pramipexole dichlorhydrate  Tablets  Prolonged release 
SINCRONIUM  Acetylsalicylic acid Simvastatin
Ramipril 
Capsules  Should be swallowed, do not open
By manufacturer 
SINERGIX  Tramadol hydrochloride ketorolac tromethamine  Tablets  Sublingualh 
SINGULAIR  Montelukastsodium  Tablets  Coatedb 
SIRDALUD MR  Tizanidine hydrochloride  Capsules  Prolonged release 
SOLUCAPS  Mazindol  Capsules  Prolonged release 
SOMAZINA  Citicolinasodium  Tablets  Coated 
SOMERAL  Alpha keto analogs of amino acids  Coated tablets  Coateda 
SPECTRACEF  Cefditorenpivoxil  Tablets  Coated 
STALEVO  Entacapone
Levodopa
Carbidopa monohydrate 
Tablets  Coatedb 
STELABID  Trifluoperazine dihydrochloride
Isopropamide iodide 
Coated tablets  Coateda 
STILNOX CR  Tartrate of zolpidem  Tablets  Prolonged release 
SUB-Z  Melatonin  Tablets  Sublingualh 
SUFISAL  Pentoxifylline  Coated tablets  Prolonged release 
SUPACID  Pantoprazole sodium sesquihydrate  Tablets  Prolonged release 
SUPRADOL  Ketorolac tromethamine  Tablets  Sublingualh 
TARDYFERON FOL  Ferrous sulfate
Folic acid 
Coated tablets  Prolonged release 
TARKA  Trandolapril
Verapamil hydrochloride 
Tablets  Do not break
By manufacturer 
TEBONIN OD  Dry extract of ginkgo biloba  Tablets  Prolonged release 
TEGRETOL LC  Carbamazepine  Tablets  Prolonged release 
TEMPOLIB  Trimebutine maleate  Tablets  Prolonged release 
TEOLONG  Theophylline  Capsules  Prolonged released 
TESAPERL  Benzonatato  Capsules  Liquid fillinge 
TEVETENZ  Eprosartanmesylate  Tablets  Coatedb 
TEVETENZ DOX  Eprosartanmesylate Hydrochlorothiazide  Tablets  Coatedb 
THIOCTACID 600HR  Thiotic acid
 
Tablets  Do not break
By manufacturer 
TIBACLIM  Tibolona
Calciumcarbonate Colecalciferol (vitamin D3
Tablets  Coated 
TOLORAN  Ketorolac tromethamine  Tablets  Sublingualh 
TOLVON  Miaserin  Tablets  Should be ingested without chewing 
TRACLEER  Bosentan monohydrate  Tablets  Coated 
TRADOL  Tramadol hydrochloride  Capsules  Should be swallowed, do not open
By manufacturer 
TRADEA  Methylphenidate hydrochloride  Tablets  Prolonged release 
TRADOL DELAYED  Tramadol hydrochloride  Tablets  Prolonged release 
TRANKITEC  Magnesium valproate  Tablets  Coatedc 
TRANSKRIP  Magnesium valproate
Hydralazine hydrochloride 
Tablets  Prolonged release 
TRIBEDOCE COMPOUND  Diclofenac sodium
Thiamine mononitrate
Pyridoxine hydrochloride Cyanocobalamin 
Coated tablets  Coateda 
TRIQUILAR  Levonorgestrel
Ethinylestradiol 
Coated tablets)  Coated 
TRUVADA  Emtricitabine
Tenofovir disoproxil fumarate 
Tablets  Coatedb 
TYKERB  Lapatinib  Tablets  Coated 
ULCEVIT  Ranitidine hydrochloride  Coated tablets  Coateda 
ULGASTRIN  Ranitidine hydrochloride  Coated tablets  Coateda 
ULPAX  Lansoprazole  Capsules  Delayed release 
ULSEN  Omeprazole  Capsules  Coatedj 
ULSEN PCS  Omeprazole  Capsules  Coatedj 
VANTOXYL  Pentoxifylline  Tablets  Prolonged release 
VICTAN  Ethyl loflazepate  Tablets  Coatedb 
VIMOVO  Naproxen
Esomeprazole 
Tablets  Delayed release 
VIVIOPTAL  Vitamins
Minerals 
Capsules  Liquid fillinge 
VOLFENAC DELAYED  Diclofenac sodium  Coated tablets  Prolonged release 
VOLTAREN DOLO  Diclofenac potassium  Capsules  Do not break
By manufacturer 
WELLBUTRIN  Anfebutamona (Bupropion)  Tablets  Prolonged release 
WOBE-MUGOS  Trypsin
Chymotrypsin
Papain 
Coated tablets  Coatedc 
WOBENZYM  Proteolytic enzymes  Coated tablets  Coatedc 
XATRAL OD  Alfuzosinhydrochloride  Tablets  Prolonged release 
XELODA  Capecitabine  Tablets  Coated 
XUZAL  Levocetirizine dihydrochloride  Tablets  Do not break
By manufacturer 
ZALDIAR  Paracetamol
Tramadol hydrochloride 
Tablets  Effervescentf 
ZAPEX  Mirtazapine  Tablets  Do not break
By manufacturer 
ZELBORAF  Vemurafenib  Tablets  Coated 
ZITROFLAM  Nimesulide
Azithromycin dihydrate 
Tablets  Coatedb 
ZOMIG RAPIMELT  Zolmitriptan  Tablets  Dispersablei 
ZYLOPRIM  Allopurinol  Tablets  Mucosal irritation 
ZYPREXA ZYDIS  Olanzapine  Tablets  Dispersablei 
ZYTIGA  Abiraterone  Tablets  Mucosal irritation 
a

Covered with sugar: masks smells and/or unpleasant flavors, protects photosensitive or easily oxidizable drugs.

b

Coated with polymer film: masks odors and/or unpleasant flavors, protects photosensitive or easily oxidizable drugs, allows a prolonged release, depending on the coating polymer.

c

Entericcoating: used for drugs that are destroyed by gastric acidity, for drugs that irritate the stomach mucose and for delayed release. They release their active substance into the small intestine.

d

Granules with slow-release coating: used for slowly or steadily releasing the active substance.

e

Capsules of soft gelatin (with liquid content): The extraction of the liquid from the interior can lead to an incorrect dosage.

f

Effervescent: designed to dissolve in water before ingesting, if chewed they lose their ability to dissolve quickly, and may present effervescence in the mouth if not dissolved in water beforehand.

g

Prolonged or extended release: If the developed system containing the dose is destroyed, the incidence of side effects or the toxicity of the drug is increased by releasing a higher dose.

h

Sublingual: intended to the drug dissolves quickly, obtains a better absorption and reaches the bloodstream in a short time.

i

Dispersible: designed to be dispersed in water before swallowing, if dissolved improperly, there may be a loss of dosage.

j

Enteric coated granules: used for drugs that are not activated by gastric acidity, for those that irritate the stomach mucose and for a delayed release. They release their active substance into the small intestine.

Discussion

Our study reveals that a large proportion of patients (80.3%) who have used tablets as a pharmaceutical form of drug administration have splitted them or crushed them, unlike the study by Quinzler et al., in which 49% of its study population split at least one drug.8 The latter results resemble a study carried out in the Netherlands at five community pharmacies, where 31% of tablet prescriptions were found to have been modified prior to administration; that is, they were splitor crushed because the prescribed dose needed to be reduced; 30% were split on the initiative of the patient, 13% because of the ease of administration and 17% because the patient chose to take a lower dose.20 In the present study, about 50% of the patients stated that the main reason was for ease of administration, while 22% stated that their reason was dose adjustment. Despite the differences in the results of the cited research and the present study, according to Rodenhuis et al., there is an important need for patients to cover these two aspects.20

Although the practice of splitting tablets is common both in outpatient settings and in hospitals and nursing homes, little is known about these patterns.27 In this study, most of the people interviewed used a knife to split the tablets, followed by using the hands, then the teeth and finally a tablet cutter. Studies indicate that the use of these cutters to facilitate the division of tablets is rare, since their use is not common because they are not available in all pharmacies.8 The study by Quinzler et al. reports that 16.3% of patients had problems with tablet division, of which 70.1% solved it using a knife or other sharp object, and only 19.4% used a cutter to split the medication.8

The practice of crushing or splitting tablets by patients can lead to health problems, since not all tablets are suitable for this purpose. Splitting prolonged or extended-release tablets may result in increased side effects and a compromise in effectiveness, given the uncontrolled release of the active ingredient, or the latter may be impaired if it is contained in enteric coated tablets or has the potential to irritate the stomach.6–8,28–32

On the other hand, it is generally considered that if the manufacturer marks a dividing line on the tablet, that means that it is fit to split. However, this is not always the case, since there is a degree of inaccuracy in breaking them due to their shape, size or type of coating which results in pieces of different sizes that can lead to fluctuations in the administered dose, especially if this occurs with narrow therapeutic window drugs, such as digoxin and warfarin, unlike drugs with broad therapeutic ranges and long half-lives, in which dose fluctuations are unlikely to be clinically significant.6,7,33 In the case of psychotropic drugs, the convenience of splitting tablets may result from clinical observation, since for patients like the elderly the prescription of complete tablets can result in over sedation in some cases. Thus, it is recommended that, if they are going to be divided by the patient, also consider the possible physical limitations, and that pharmacists give appropriate counseling regarding the necessary tools to do it the right way.34,35

Other studies reveal positive aspects of the practice of breaking tablets, such as the economic benefit that both the patient and health institutions generate by reducing their costs by up to 50%, due to the fact that the costs of the drugs frequently decrease when the dose is increased, independently of this.11,13,36

The decision to split tablets should be made after reviewing the relevant considerations. The following recommendations can be used as a guide.6,26

  • Use liquid dosage forms of the same medicines. If they are not available, consult your pharmacist to determine if extemporaneous (compounding) preparations can be made. Occasionally, the injectable form of the medication can be used by placing the appropriate amount of medication in a liquid as a juice. This should be done after consulting the pharmacist to ensure there are no compatibility problems or changes in absorption of the active ingredient.

  • Check the product information before recommending that it be broken or crushed.

  • Use a tablet cutter to improve accuracy. However, patients should be instructed in their proper use.

  • Advise patients about the proper storage of tablet fragments.

In conclusion, we found that there is an urgent need to improve information about which pharmaceutical forms can be splitted, divided or crushed. The work of pharmacists and health professionals is critical in educating patients about how prescribed drugs should be administered, as well as providing relevant information and indications, with emphasis on aspects related to their use, administration, and conservation, with the goal of avoiding medication errors. Pharmaceutical companies should more clearly label presentations of drugs so that patients can recognize those that should not be splitted or crushed.

Ethical disclosuresProtection of human and animal subjects

The authors declare that no experiments were performed on humans or animals for this study.

Confidentiality of data

The authors declare that no patient data appear in this article.

Right to privacy and informed consent

The authors declare that no patient data appear in this article.

Funding

No financial support was provided.

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgement

To the hospitals for the facilities provided for the application of the surveys.

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