Tablet Crushing Considerations in Geriatrics
M. Fodil a,∗ , A. Fillette b, C. Trivalle c
a Pharmacist practitioner attached. Pharmacy Department, Paul-Brousse University Hospital, AP—HP, 14, avenue P.V.-Couturier, 94804 Villejuif cedex, France b Pharmacy intern. Pharmacy Department, Paul-Brousse University Hospital, 14, avenue P.V.-Couturier, AP—HP, 94804 Villejuif cedex, France c Geriatrician, hospital practitioner. Department of Geriatrics, Paul-Brousse University Hospital, AP—HP, 14, avenue P.V.-Couturier, 94804 Villejuif cedex, France
Summary: In geriatrics, it is common to have to crush tablets to facilitate medication intake in patients with swallowing and/or behavioral disorders. However, this operation can significantly alter the effectiveness of drugs, their pharmacokinetics and even lead to toxic effects for both patients and caregivers. All pharmacological classes are concerned. In order to avoid potential iatrogenic and occupational risks, it is important to make sure of the galenic formulation beforehand, as some drugs prohibit any manipulation. We offer a simplified list of drugs for which it is forbidden to crush them and practical recommendations.
© 2012 Published by Elsevier Masson SAS.
In geriatrics, whether at home, in an institution or in a hospital, the rule is to always favor the oral route, including for medication. For this purpose, drugs are presented in various dosage forms, of which tablets and capsules are the most common. Each dosage form corresponds to different pharmacokinetic properties (absorption, diffusion, active ingredient levels, etc.), compliance with which ensures the full pharmacological effect of the molecules. However, tablet crushing is a common and sometimes unavoidable practice in patients with swallowing and/or behavioral disorders. This also happens frequently for patients with a nasogastric tube (NGS) or gastrostomy. However, this manipulation can be the cause of avoidable drug iatrogeny (adverse effects and / or therapeutic ineffectiveness) if certain recommendations are followed. Thus, before any modification of a pharmaceutical form, it is essential to check the type of galenic formulation and to check whether crushing is authorized. In cases where this manipulation is prohibited, an alternative must be sought. In general, modified-release forms (delayed or prolonged, gastroresistant or coated) should not be crushed; crushing destroying the finality of their galenic preparation. In most cases, the risk is mainly to be ineffective, but some molecules have a specific toxicity.
A study conducted in June 2009 at Rouen University Hospital  showed that 42% of the drugs crushed had a dosage form that contraindicated crushing. In addition, the equipment used (a mortar in 92.6% of cases) was common to several patients in 59.4% of situations. Equipment was cleaned between each preparation in only 11.6% of cases. Medications from the same patient were mostly crushed together (74.4%).
In a study conducted on a given day at PaulBrousse Hospital in a geriatric ward (61 follow-up care and rehabilitation beds and 62 long-term care beds), we counted 49 types of crushed tablets. Nine tablets (13%) should not be crushed, including alendronate tablets that have oral and esophageal toxicity.
These data confirm the frequency of this practice in geriatric settings and reinforce the need to develop specific recommendations for each drug and protocols for crushing procedures. There are now many lists of recommendations for oral medications. The first France list targeting drugs that can be administered by tube was proposed in 1999 by the University Hospital of Nîmes . There are others available on the Internet . Recently, the “Circuit du Médicament” group of the Observatory of Drugs, Medical Devices and Therapeutic Innovation (OMEDIT) of Haute-Normandie published a list of tablets, capsules and capsules that can be crushed. . If this manipulation is not recommended, alternatives are also proposed. The HAS guide to “safety and self-assessment of drug administration”  recommends making a list of tablets that can and cannot be crushed. Some private groups of residential facilities for dependent elderly people (EHPAD) have also written their own booklet of the drug .
However, while all these sources of information are often intended to be exhaustive and relatively easy to access on the Internet, they are often difficult to use. Thus, after a reminder of the different dosage forms on the market, we present simplified lists of drugs for which crushing and opening are prohibited, with particular emphasis on potentially toxic molecules. Finally, we offer practical recommendations regarding crushing tablets. We have deliberately chosen to present medicines using their trade names rather than the International Nonproprietary Name (INN) because the specificities of galenics can be very different for the same active ingredient from one laboratory to another, including generic forms.
Reminders on galenics
- physicochemical criteria (stability of the active ingredient, incompatibility. . .);
- pharmacokinetic criteria (release of the active ingredient, bioavailability. . .);
- pharmacodynamic criteria (initial dose, duration of effect, etc.);
- the criteria of comfort and commercial (taste, comfort of the socket, color . . .).
For capsules, whether “conventional”, extended-release (LP) or delayed-release, they can most often be opened (if mentioned in the summaries of product characteristics [SmPC]) and their contents mixed with food or drink (preferably water) ensuring that the integrity of their contents (e.g. micro granules) is preserved (do not chew them, neither chew nor grind them). Only capsules with toxic content should not be opened (especially chemotherapy) and gastro-protected capsules (e.g. Cymbalta®). For Modopar®, the patient must swallow the capsule whole, without chewing or opening it. In addition, the absorption of Modopar® can be modified by meals, so it is recommended, as much as possible, to take it at least half an hour before or one hour after the meal. For soft capsules, they should not be opened because they usually contain an oily suspension (example of Tadenan®).
Conventional release tablets (uncoated and coated)
A conventional tablet is defined as a solid preparation containing a single dose of one or more active ingredients obtained by squeezing a uniform volume of powdered particles. . The active substance(s) are dispersed in one or more excipients (substances without therapeutic activity) to facilitate tablet preparation. Depending on their nature, excipients play different roles: binders, thinners, disintegrants or lubricants. [8,9]. In some formulations, certain colors and flavors may also be added to enhance appearance or mask an unpleasant taste..
They can be scored for dosage adjustment and crushed for easy taking. They disintegrate quickly (about 15 minutes) and come in different forms: dispersible, oro-dispersible, sublingual, sucking, effervescent or classic.
The coating protects the active ingredient from light, masks an unpleasant taste, taste or smell and facilitates the administration of the drug. Aromatizing a molecule to make it acceptable is a decisive operation for treatment adherence. In addition, the aroma participates as an excipient in masking the taste of certain active ingredients. The product is sweetened with sucrose or other permitted sweeteners and then flavoured; banana, tangerine, mint, lemon . . .
The coating can be of different types: dredification, lamination, filming. The sugar-coated tablets are coated with sugar and the film-coated tablets are coated with a thin-layer film-former. Film coating consists in coating an active ingredient with film-forming agents thus forming a film devoid of pharmacological action, homogeneous smooth, often shiny and possibly colored.The coating is generally applied to all solid oral forms, such as tablets, soft capsules, capsules, granules and microgranules . The gastro-resistant coating ensures the protection of the active ingredient from the action of digestive juices, the active ingredient being released in the intestine.
Coated tablets (Table 1) are never scored and have a longer disintegration time which depends on the type of coating: sweet coating less than or equal to 60 minutes and film-coated less than or equal to 30 minutes.
The European Pharmacopoeia defines modified-release tablets as “tablets, coated or uncoated, which are prepared with special excipients, or by particular processes, aimed at changing the rate, place or time of release of the active substance(s)”. Coating with a polymer is one of the methods of obtaining a modified release form where the rate of release of the active ingredient, is, in this case, inversely proportional to the thickness of the film [11,12].
LP dosage forms (Table 2) are designed to reduce the frequency of administration and maintain more stable effective plasma concentrations of the drug (absence of plasma peaks responsible for side effects), thus ensuring a more consistent pharmacological effect. They allow the maintenance of therapeutic concentrations of the drug for up to 12 hours or more. Excipients, film-coating or special coating allow the active substance to be released gradually throughout the digestive tract. Less frequent administration is more convenient and generally improves adherence to treatment. The release of the active ingredient can also be discontinuous, different doses are then released successively. The crushing of these LP forms is strictly prohibited because it would result in an excessive release of the active ingredient that can cause overdose and toxic effects. On the other hand, the LP does not systematically prohibit secability; in this case, the SPCs shall explicitly mention this.
Tablets with microgranules (pellets)
The tablets consist of a multitude of pellets surrounded by a film controlling the release of the active ingredient. For example, after administration of Metoprolol®, the tablet decays into numerous pellets that release the molecule continuously for 20 hours.
These are usually triple-layer tablets. The action is two-phase, the middle layer serving only as an insulator. This formulation (dual release [DR]) makes it possible to have a loading dose and a maintenance dose for the same active ingredient. This system is not used in France, but exists for Xatral® and Modopar® for example.
The Oros Push Pull system is used to make these tablets (example: Chronadalate®). They are coated with cellulose acetate making a semi-permeable membrane which is subsequently pierced with a micro-orifice visible on the surface of the tablet. The core is a bilayer tablet whose upper part contains, among other things, the active ingredient and the lower part an osmotic agent (sodium chloride) and cellulose derivatives. Upon contact with gastric fluid, water diffuses inside both parts of the tablet through the semipermeable membrane. The compartment containing the osmotic agent swells by absorption of water and pushes the active ingredient out of the tablet. The membrane remains intact, it is excreted in the form of a flaccid shell. These tablets ensure a regular release of the active ingredient over 12 hours.
Delayed or delayed release forms
These dosage forms (Table 3) use coatings called gastro-resistant or enteric to maintain the integrity of the active ingredient until it is released into the intestine. This formulation concerns active ingredients irritating to the stomach (example: acetylsalicylic acid), destroyed in an acidic medium or allows to bring an active ingredient directly to its site of action. Oral administration of colonic-release dosage forms protects the active ingredients from potential degradation in the stomach and/or small intestine. In some pathologies, it is essential that the active ingredients arrive at the site of absorption. The targeted delivery of the active substance to the colon is indicated in:
- local treatment of colon pathologies (Crohn’s disease, ulcerative colitis. . . );
- chronotherapy for conditions such as asthma, hypertension, arthritis, cardiac arrhythmia or inflammation;
- unstable active substances in the first part of the digestive tract.
The grinding of these dosage forms could therefore cause gastric adverse effects (depending on the active ingredients) and / or a loss of therapeutic activity.
Accelerated release forms
For this type of formulation, grinding has no interest given the galenic which does not lend itself to it. This category includes effervescent, sublingual and orodispersible tablets. Orodispersible tablets (e.g. Aricept®, Zyprexa® Velotab, Dafalgan® Odis) should be placed on the tongue. They are of interest especially during swallowing difficulties. Sublingual tablets (example: Trinitrine®) must be kept under the tongue where they are absorbed.
Drugs with a narrow therapeutic range
The notion of a drug with a “narrow therapeutic range” means that any variation in its concentration in the body, even slight, can lead to undesirable, potentially serious effects or its ineffectiveness. In other words, the minimum effective dose is very close to the maximum tolerable dose. Their handling requires particularly careful monitoring. As it is difficult to maintain plasma concentrations in the therapeutic range, crushing these drugs is not recommended (Table 4).
Cytotoxic, immunosuppressive, toxic and irritant drugs
The grinding of these drugs represents a toxic risk to the person handling them and can cause occupational accidents (Table 5). Some have toxicity to the patient himself. Pregnant women (caregivers, nurses) should be warned of the risk of handling all teratogenic drugs such as Chibro-Proscar®.
Fosamax® and Fosavance® tablets should not be crushed as they may cause oral and esophageal ulcerations. The active substance is highly irritating, therefore the tablets should be swallowed whole while standing with a full glass of water. Regarding Glivec® and Methotrexate®, the crushing can cause accidental inhalation of the “airborne” powder but also a deposit on the different places of the body (hands, arms, face, eyes) and could have harmful consequences on the health of the medical staff who handle them.
For Art® 50, it is not recommended to open the capsules because diacerin is potentially irritating to the oral and esophageal mucosa.
Avodart® has a teratogenic effect in pregnant women. The capsules should be swallowed whole, and should not be chewed or opened as contact with the contents of the capsule may cause irritation of the oropharyngeal mucosa. The capsules can be taken with or without food.
Temodal® capsules should be swallowed whole with a glass of water. They must not be opened or chewed. If the capsule is damaged, avoid contact with the skin, eyes or nose. If this happens, it is necessary to thoroughly wash the affected area with water.
If it is necessary to open Hydrea® capsules, protective gloves and a mask should be worn and the necessary precautions should be taken to avoid contact with the skin or mucous membranes.
Exelon® capsules should be swallowed with a beverage, without opening or crushing them, as they may cause local irritation if opened. In case of oral administration difficulties, it is best to use the oral solution (2 mg/mL) or transdermal patches that release 4.6 mg or 9.5 mg rivastigmine for 24 hours.
The decision to crush a tablet should always be evaluated by a doctor after checking the RCPs (Vidal dictionary) and the various lists available on the internet or in the literature [3—5]. This is a case-by-case decision and do not hesitate to consult your pharmacist, or even the pharmaceutical laboratory in case of doubt. In addition, the restrictions are not the same depending on whether the drug is administered orally or by tube. In this article we consider only molecules given by mouth. The main rules to be followed are summarized in Table 6.
Any modification of the dosage form may lead to a change in the release and absorption profile of the active ingredient. This change may affect the safety and/or effectiveness of the drug. The main risks, if these recommendations are not followed, are dosing errors (under or overdose), risks of local toxicity with irritation or mucosal ulceration, or even a teratogenic risk for pregnant women who handle these treatments and finally changes in pharmacokinetic or pharmacodynamic properties. The active ingredient may be released in an accelerated way (e.g. for delayed forms) or, conversely, the pharmacological activity decreased (e.g. for gastro-protected tablets). In a number of cases, this data is missing and as a precaution, it is better to consider that handling is not recommended.
When the medication cannot be crushed or the capsule opened (the package leaflet usually says “should not be chewed or crushed” or “should be swallowed whole”), another alternative should be sought.
To crush a tablet, one “crusher-grinder” system should be used per patient , hand washing before and after handling, administering the drugs one by one (otherwise there is a risk of chemical interactions), immediately after crushing (otherwise, risk of degradation of the active product) and washing the device after each operation. If it is a pestle and mortar system, it must be rinsed with water between each use. Indeed, in the absence of cleaning drug particles can be administered to another patient. In addition, the person who crushes must put on gloves of systematic way (allergic risk) and a mask for toxic products.
Intermediate containers should be avoided and the medication (water) should be used as neutral as possible . Thus, some drugs should not be mixed with milk (e.g. Ciflox®), for others (even when they are not crushed) they should not be administered with grapefruit juice (cytochrome-P450 interactions) and others may be sensitive to heat (destruction of the active ingredient).
It is important to train doctors and nurses in these good practices regarding the use of drugs in geriatrics.
The sharing or crushing of a tablet must be decided on a case-by-case basis, depending on the galenic properties of the preparation, the stability and the therapeutic margin but also the toxicity of the active ingredients. Indeed, modifying a dosage form can modify the stability and bioavailability of the active ingredient, its rate of release, the duration of the therapeutic effect, or even lead to incompatibilities or reveal uncomfortable bitterness for the patient. In addition, the modification of a galenic formulation has a certain impact on the dissolution and / or absorption of the active ingredient and, consequently, on the therapeutic effect and may be the cause of drug iatrogeny.
Knowing the tablets not to be crushed should reduce the iatrogenic risk in geriatrics. We hope that this simplified presentation will facilitate the work of geriatric teams in their daily management of medications.