The Role of the Pharmacist in Selecting the Best Choice of Medication Formulation in Dysphagic Patients

Usually, the administration of drugs by feeding tube in dysphagic patients involves handling of marketing licenses outside their term, due to the lack of suitable formulations. This circumstance has put health professionals in the dilemma of choosing the formulation whose manipulation possibly does not alter the effectiveness of the drug. In this regard, a practical guide providing indications on the prescription, handling, and administration of drugs through enteral feeding tube could be of paramount utility. For this purpose, we have considered the 1047 solid oral pharmaceutical forms included in the formulary of San Paolo Hospital (Savona, Italy). From our analysis, it emerges that 95% of medicinal products are worryingly used off-label and 40% have to be managed by the hospital pharmacists without having suitable indications by either the manufacturers or by literature studies. To fill this gap, we have compiled a detailed table containing missing indications derived from pharmacist expertise and evidence-based practices, with the aim that the sharing of our procedures will contribute to make uniform pharmacological therapies from one hospital to another. This study will allow doctors to have easy access to information on drugs that can be prescribed and nurses to become familiar only with the pharmaceutical forms that can be administered.


Introduction
In the past, interest in enteral nutrition (EN) was rather low, due to the introduction of new and safer parenteral administration techniques. However, in the last two decades, EN through percutaneous endoscopic gastrostomy (PEG) has been reevaluated as a valid metabolic rebalancing therapy, both by virtue of an improvement in the quality of the tubes and nutritional mixtures used. Additionally, thanks to the recent dietary and physiological acquisitions of the digestive system, a more correct overview of the limitations of total parenteral nutrition (TPN) has been achieved [1][2][3]. According to the guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) on EN in adults [4], in all the conditions in which an indication for artificial nutrition (AN) is present and where there is normal functioning of the gastrointestinal tract with the possibility of covering needs by the enteral route, EN should be considered the first choice nutritional technique. In fact, it has been demonstrated that EN is simpler, more physiological less expensive, and safer than TPN, since it avoids the risks of venous catheter infections [5]. Furthermore, it is therapeutically superior to TPN, as the nutrients perform a direct trophic action on the intestinal lumen by inducing the release of trophic hormones and supporting the structural and functional integrity of the intestinal mucosa, which seems essential for maintaining immune function [6]. In our territory, managed by the local health authority ASL 2 Savonese (Liguria, Italy), the data are confirming this trend, as from 2019 to 2021, the hospitalized  Other eminent sources considered were the practical guidelines from the Società Italiana di Nutrizione Artificiale e Metabolismo (SINPE) and European Society for Clinical Nutrition and Metabolism (ESPEN). In particular, the SINPE guideline on Nutrizione Artificiale Ospedaliera [8] and the ESPEN guideline on home enteral nutrition [9]. In addition, since administration via tube is a route that in most cases is not provided for in the SmPC, some information has been extrapolated by consulting the Handbook of Drug Administration via Enteral Feeding Tubes on behalf of the British Pharmaceutical Nutrition Group [10] and reading published studies present in the literature (PubMed database). Finally, indications of use were established also by analyzing the list of excipients employed by the producer. In these instances, the directions provided are based on the pharmacist's practical experience and knowledge. The sources chosen to evaluate the suitability of drug administration via tube are summarized in Table 1 in hierarchical order. Table 1. Sources chosen to evaluate the suitability of drug administration via tube and their level of reliability in decreasing order. The sources of the information are highlighted in different colors according to their level of reliability. Green, level A (SmPC); light blue, level B (Guidelines); pink, level C (literature); yellow, level D (pharmacist know-how).

Source
Level of Reliability Summary of product characteristics A European and Italian guidelines on artificial nutrition B Research studies available in the literature C Hospital pharmacist know-how D For each solid oral drug formulation listed in the hospital formulary, the Anatomical Therapeutic Chemical (ATC) Classification System, the name of the API, the trade name, the manufacturer, the pharmaceutical form, if the product can be administered via tube or not, instructions for handling, and finally the sources of the information are highlighted in different colors according to their level of reliability. An attempt was made to provide as much information as possible: the events that the administration by tube can be carried out, when to administer the drug, compatibility between the drug and EN, and the presence of some particular excipients (e.g., alcohol).
Since the use of oral liquid pharmaceutical forms creates a minimal risk of tube obstruction and ensures adequate absorption of the drug, a switch from a solid oral formulation to a corresponding one in liquid form was considered advisable whenever possible. However, the liquid formulations may be hyperosmolar and require appropriate dilution. The volume of water (V) to be added has been calculated with the following formula: where mOsm desired is 300-500 mOsm/kg, mOsm initial is the osmolality of the pharmaceutical product, V i is the volume of the liquid pharmaceutical product before handling, and V f is the volume of the final product with the desired osmolality.
To complete our study, we reported the most numerous extemporaneous liquid preparations intended to be administered by PEG to patients in the Neurology, Internal Medicine, and Otorhinolaryngology departments of the San Paolo Hospital in Savona.

Drug Formulations for Administration by Tube: The Pivotal Role of the Pharmacist
The therapeutic process is defined as the sum of several phases, including drug procurement, storage, preservation, stock management, prescription, preparation, administration, and the evaluation of side effects and/or benefits (Italian Ministry of Health, recommendation n. 7 for the prevention of death, coma, or severe damage arising from errors in drug therapy) [11]. Such definition evidences that there may be numerous factors that can lead to an unreliable therapy, and meanwhile health-care professionals must be able to ensure that the hospitalized patients receive the appropriate drug in the correct pharmaceutical form and route of administration. Specifically, the skills of the hospital pharmacist, in the context of preventing errors in therapy, could play a key role in evaluating the correct and safe use of drugs, both in the prescription and in the administration phase. In fact, it has been already demonstrated that pharmacy intervention can significantly reduce the number of errors related to administering medication through the enteral feeding tube with minimal additional workload [12].
Nowadays, the need to carry out a correct manipulation of oral drugs to be administered to patients subjected to EN is an increasingly emerging problem. Before deciding whether to modify the original pharmaceutical form in any way, the compounding pharmacist refers to SmPC, but, unfortunately, the clinical studies on the bioavailability of oral pharmaceutical forms performed by the companies rarely consider administration via artificial tubes. In most cases, manufacturers lack data to support the chemical stability of tablets when crushed and dispersed in water prior to use, and there are no studies comparing the efficacy or bioavailability of split and crushed solid pharmaceutical forms, which means that no company feels able to provide recommendations on the use of drugs by means of a tube. In this study, we contacted 124 pharmaceutical companies to obtain more detailed information on drug stability after crushing or switching routes of administration. Unfortunately, only one company (0.8%) gave us further information. In most cases, companies only suggested referring to the SmPC. Indeed, drug stability assessment performed by pharmaceutical companies generally involves the testing of the drug substance or drug product using a stability-indicating method in order to establish the retest period (for premarket stability) and shelf life (for commercial stability). Since the companies had not carried out any evaluation of the stability of the drug after handling and/or change of administration route, they avoided taking any kind of responsibility in giving us advice. However, before resorting to off-label use, the general indications stress first of all evaluation of the existence of formulations suitable for alternative routes to oral administration. Table 2 shows APIs for which there are multiple options of routes of administration.
When such alternatives are not suitable, as indicated in the column of limitations, or only oral formulations are available, the PEG also becomes a unique access route for drug administration. In these cases, the SINPE guideline for Hospital Artificial Nutrition states that the administration of drugs by enteral tube preferably requires the use of liquid pharmaceutical forms, when available, or as a last resort the trituration of the solid forms and their dispersion in a suitable solvent [8]. It must be considered that switching from one formulation to another may involve dose adjustment and careful monitoring of the plasma levels of the drug for imperfect equivalence between the different formulations (e.g., liquid phenytoin vs. tablets) [13]. This raises a number of issues regarding the responsibility of such administrations and of any adverse effects that the patients may experience.
Many members of health-care teams, especially pharmacists, are in a position to raise the awareness of potential drug-nutrient interactions and incompatibilities that may derive from the off-label use of a drug. Pharmaceutical incompatibility arises in dosage forms where the release of API is controlled by enteric or delayed coatings. In these cases, the manipulation (i.e., trituration) of the medicinal product leads to an immediate release and absorption of the API with overdose at the start of treatment and subtherapeutic dosages thereafter. As shown in Figure 2, modified-release tablets are the fourth most numbered formulation and all the modified-release solid oral formulations, including gastroresistant ones, represent the 12% of the total medications included in the Savona hospital formulary.
Pharmacological incompatibility manifests itself with an alteration in pH, motility, or gastrointestinal secretions resulting from a pharmacological effect of the drug and generally alters the tolerance or absorption of enteral nutrition and/or the absorption of other drugs administered in polypharmacy. It is the case of drugs with anticholinergic effect that relax smooth muscle and inhibit gastric motility, such as antihistamines (promethazine, diphenhydramine, etc.), tricyclic antidepressants (amitriptyline, imipramine, maprotiline, trimipramine, etc.), phenothiazines (chlorpridomazine, etc.), and antiparkinsonians (biperidene, trihexyphenidyl, bornaprine, orphenadrine, etc.). Pharmacokinetic interactions can occur following the simultaneous administration of drugs and EN blends since the nutritional mixtures can alter the processes of release, absorption, distribution, metabolism, and excretion of drugs, which, in turn, can alter the kinetics of nutrients. Clinically, the most significant drug-enteral feeding interactions concern phenytoin and carbamazepine. The greatest number of compatibility studies with EN preparations have been performed for phenytoin [14]. The plasma levels of the drug were lower (70-80%) when administration was associated with EN, while they increased when EN was interrupted 2 h earlier and restored 2 h later. The mechanisms proposed were different, from the joining of the drug to the proteins or electrolytes of the nutrition mixture to the alteration of the solubility. It was observed that the interaction was more evident when phenytoin was introduced directly at the jejunal level, perhaps due to a decrease the time of intestinal transit. It is well known that the absorption of theophylline varies according to the composition of the diet; therefore, to avoid a 60-70% decrease in drug absorption, due to the increased metabolism that some diets (rich in proteins and low in carbohydrates) cause, it is necessary to suspend enteral feed at least 1 h before administration and restore it 2 h after. For the sake of completeness, we point out that some drugs are optimally absorbed only on an empty stomach (e.g., tetracyclines, penicillins, rifampicin, verapamil, atenolol, captopril).
Pharmacodynamic interactions occur when alterations in the action of the drug are related to pharmacological antagonism at the receptor site. The vitamin K content of nutritional preparations can determine an antagonism towards the therapeutic action of oral anticoagulants, such as warfarin. Initially, it was thought that this antagonism was only to be attributed to the quantity of vitamin K contained in the nutritional mixtures and therefore preparations with low doses of the same (less than 75-78 mg/1000 kcal) were recommended. Recently, this antagonism has also been observed for preparations with minimal contents of vitamin K and therefore the decrease in the therapeutic effect of the drug has been related to an alteration of its absorption probably attributable to its union with soy proteins and caseinates. This makes monitoring the prothrombin time necessary to guarantee the anticoagulant effect, as well as the indication to prefer heparin in critical clinical conditions [15]. Pharmacological incompatibility manifests itself with an alteration in pH, motility, or gastrointestinal secretions resulting from a pharmacological effect of the drug and generally alters the tolerance or absorption of enteral nutrition and/or the absorption of other drugs administered in polypharmacy. It is the case of drugs with anticholinergic effect that relax smooth muscle and inhibit gastric motility, such as antihistamines (promethazine, diphenhydramine, etc.), tricyclic antidepressants (amitriptyline, imipramine, maprotiline, trimipramine, etc.), phenothiazines (chlorpridomazine, etc.), and antiparkinsonians (biperidene, trihexyphenidyl, bornaprine, orphenadrine, etc.).
Pharmacokinetic interactions can occur following the simultaneous administration of drugs and EN blends since the nutritional mixtures can alter the processes of release, absorption, distribution, metabolism, and excretion of drugs, which, in turn, can alter the kinetics of nutrients. Clinically, the most significant drug-enteral feeding interactions concern phenytoin and carbamazepine. The greatest number of compatibility studies with EN preparations have been performed for phenytoin [14]. The plasma levels of the drug were lower (70-80%) when administration was associated with EN, while they increased when EN was interrupted 2 h earlier and restored 2 h later. The mechanisms proposed were different, from the joining of the drug to the proteins or electrolytes of the nutrition  The best choice of a formulation to be administered via tube could be represented by a liquid one. Indeed, the liquid formulations can be easily administered with sufficient tranquility by means of a tube and generally they are immediately diluted in gastric juices and promptly absorbed. However, the assumption that liquid formulations are the first choice may be questionable. Cosolvents, such as ethanol, glycerol, and propylene glycol, may be present in all drug formulations being used and the acceptable daily intake (ADI) may be easily exceeded. Therefore, before shifting from a solid dosage form to a liquid, it is recommended to consider this worrying issue, i.e., ranitidine syrup (Ranidil 150 mg/10 mL) [16].
Another noteworthy aspect relates to the osmolality of liquid formulations, which is one of the physical characteristics that most affect individual tolerance to a preparation. Osmolality values close to those of intestinal secretions are better tolerated (100-400 mOsm/kg H 2 O) [13]. Formulations having osmolality values higher than 6000 mOsm/kg H 2 O) if administered without dilution could cause intolerance phenomena, especially if introduced at high speed or with tubes located in the duodenum or jejunum. This type of interaction is sometimes misinterpreted as the symptoms tend to be attributed to an intolerance to nutritional support or to gastrointestinal infections resulting in an incongruous interruption of the enteral feeding. Sorbitol is a case in point. Sorbitol is a common excipient of liquid formulations, often used as a stabilizer and sweetener. High amounts (>10 g/day) can cause intraluminal production of gas and abdominal tension, and, at higher doses (>15 g/day), important secondary effects, such as abdominal spasms and diarrhea. Pharmaceutical forms with a high sorbitol content include iron protein succinylate oral solution (Rekord Ferro 40 mg/15 mL) [17] and acyclovir oral suspension (Aciclovir Dorom 400 mg/5 mL) [18]. In cases where antiviral therapy at 400 mg five times a day is required, it is easy to exceed sorbitol ADI. Mannitol may provide the same undesirable reactions. This often happens when using the oral route for medicinal products with exclusive parenteral indication. In routine practice, when the osmolality of the preparations is not known, it is advisable to dilute the medicine with at least 30 mL of water to make the administration in the stomach compatible, thus preventing diarrheic phenomena by osmotic effect. Moreover, some suspensions and syrups may be too viscous and lead to the obstruction of the tube, such as clotrimoxazole, amoxicillin-clavulanic acid, which should always be diluted with at least 100-150 mL of water and introduced through tubes of appropriate diameter. These drugs, in fact, in addition to the risk of obstruction, have a high tube-crossing time that leads to a delay in the administration time, resulting in a possible decrease in the dose effectively administered.
Also, formulations in drops are frequently hyperosmolar (e.g., clonazepam, digoxin), and the amount of water used for drug dilution must then be obviously counted in the water-electrolyte balance. In some cases, their administration is not recommended for the adhesion of the drug to the plastic walls of the tube, resulting in therapeutic ineffectiveness (e.g., diazepam [19], carbamazepine suspension [20]). Some other liquid medical solutions cause gastric motility to slow down, and the formation of insoluble gelatins in the presence of acids predispose to the formation of bezoars (indigestible deposits that can form in the stomach). In patients in coma, sedated or with altered state of consciousness and with gastroesophageal reflux, such aggregates can cause obstruction of the esophagus with sometimes impossibility of removal of the enteral probe itself (e.g., liquid sucralfate) [21].

Solid Formulations
Recommendation n.19 by the Italian Ministry of Health deals with the risks related with the crushing and splitting of oral solid formulations [22]. Capsules and tablets require necessarily manipulation for their administration via PEG tube. In addition, particular attention should be paid to the choice of enteral mixtures, because those characterized by a high protein concentration, especially containing caseinates, interact with numerous drugs, and, due to the high viscosity, cause clots obstructing the tube. Once again, to avoid tube obstruction, it is the responsibility of the pharmacist to carefully evaluate the components of the formulation (Figure 3).
Regarding the methods of administration via PEG, it should be noted that the infusion technique is very influential. In fact, the continuous-release mode (even if conducted with pumps) more frequently predisposes to clogging of the tubes because it does not allow washing between meals, as well as not leaving free margins for drug absorption in the fasting state. Therefore, bolus and intermittent techniques are preferable. For flushing the tube, no solution has been shown to be superior to water in preventing occlusion. Obstruction may arise also from inadequately crushed tablets, precipitate formation caused by interaction between feed and drug formulation, or between drugs, and consequently it is always suggested to give each API separately, avoiding the fixed formulations [23,24]. In addition, many known interactions between drugs and conventional foods are also applicable to EN. For example, amoxicillin and digoxin are adsorbed to the fiber contained in nutritional mixtures, aluminum salts induce the precipitation of dietary proteins, tetracyclines and ciprofloxacin form complexes with calcium, paracetamol is adsorbed by pectins, and phenytoin and warfarin bind to proteins [25]. stomach). In patients in coma, sedated or with altered state of consciousness and with gastroesophageal reflux, such aggregates can cause obstruction of the esophagus with sometimes impossibility of removal of the enteral probe itself (e.g., liquid sucralfate) [21].

Solid Formulations
Recommendation n.19 by the Italian Ministry of Health deals with the risks related with the crushing and splitting of oral solid formulations [22]. Capsules and tablets require necessarily manipulation for their administration via PEG tube. In addition, particular attention should be paid to the choice of enteral mixtures, because those characterized by a high protein concentration, especially containing caseinates, interact with numerous drugs, and, due to the high viscosity, cause clots obstructing the tube. Once again, to avoid tube obstruction, it is the responsibility of the pharmacist to carefully evaluate the components of the formulation (Figure 3).  Regarding the methods of administration via PEG, it should be noted that the infusion technique is very influential. In fact, the continuous-release mode (even if conducted with pumps) more frequently predisposes to clogging of the tubes because it does not allow washing between meals, as well as not leaving free margins for drug absorption in the fasting state. Therefore, bolus and intermittent techniques are preferable. For flushing the tube, no solution has been shown to be superior to water in preventing occlusion. Obstruction may arise also from inadequately crushed tablets, precipitate formation caused by interaction between feed and drug formulation, or between drugs, and consequently it is always suggested to give each API separately, avoiding the fixed formulations [23,24]. In addition, many known interactions between drugs and conventional foods are also applicable to EN. For example, amoxicillin and digoxin are adsorbed to the fiber contained in nutritional mixtures, aluminum salts induce the precipitation of dietary

Analysis of the Solid Oral Formulations Present in the Hospital Formulary
From the analysis of the solid oral formulations of the 701 drugs included in the hospital formulary, 339 (48%) cannot be crushed or administered via tube; however, for 211 of these (30%) alternative dosage forms or other routes of administration are possible ( Figure 4). For the remaining 52% of active ingredients, however, their suitability for administration via PEG was found, but only for 5% of these, the possibility of crushing the tablet into a fine powder or opening the capsule in patients unable to swallow is indicated in the SmPC. This means that 95% of the drugs are given outside the terms of their product license.
J. Pers. Med. 2022, 12, x FOR PEER REVIEW 10 of proteins, tetracyclines and ciprofloxacin form complexes with calcium, paracetamol is a sorbed by pectins, and phenytoin and warfarin bind to proteins [25].

Analysis of the Solid Oral Formulations Present in the Hospital Formulary
From the analysis of the solid oral formulations of the 701 drugs included in the hos tal formulary, 339 (48%) cannot be crushed or administered via tube; however, for 211 these (30%) alternative dosage forms or other routes of administration are possible (Figu 4). For the remaining 52% of active ingredients, however, their suitability for administrati via PEG was found, but only for 5% of these, the possibility of crushing the tablet into a fi powder or opening the capsule in patients unable to swallow is indicated in the SmPC. Th means that 95% of the drugs are given outside the terms of their product license. Medication management is not so obvious. It often represents an area in which the can be many differences from one hospital to another due to the lack of standardized pr tocols. At San Paolo Hospital in Savona, the key role played by the hospital pharmacist particularly evident from Figure 5, where the pharmacist's expertise in administering Medication management is not so obvious. It often represents an area in which there can be many differences from one hospital to another due to the lack of standardized protocols. At San Paolo Hospital in Savona, the key role played by the hospital pharmacist is particularly evident from Figure 5, where the pharmacist's expertise in administering a feeding tube therapy is necessary for the management of 40% of the formulations present in the hospital formulary. These data arose from the analysis of Table 3, which contains embedded all the collected information. Particularly, the different colors, both in Figure 5 and in Table 3, are indicative of the sources behind the decisions on the feasibility of using a solid pharmaceutical form administered by tube, and each color refers to a level of reliability, as reported in Table 1.  The practical suggestions embedded in Table 3 are partly available in the SmPC or were supplied by the companies at our request (green lines), partly present in the literature (pink lines), partly suggested by guidelines (light blue lines), and partly developed in the hospital pharmacy according to pharmacists' knowledge (yellow lines). When the SmPC does not include information about the change in administration route, the suitability of a formulation to be administered via tube was taken, firstly considering the SINPE and ESPEN guidelines, where it is clearly stated that it is dangerous to break up prolongedrelease drugs (retard formulations) or gastroresistant preparations, whose manipulation can cause overdoses or reduction of the therapeutic effect. Moreover, if the drug is in form of soft capsules, it is not possible to crush them nor is it advisable to pierce them to suck the content. The guidelines also suggest switching from the oral solid dosage form to the corresponding liquid form where possible and to administer one drug at a time. If any of these conditions are present, the pharmacist has to act accordingly (light blue lines). Instead, pink lines are representative of drugs, whose administration via tube was already experienced and reported in the literature, while the yellow colored lines report all cases where the pharmacist's experience is essential to the preparation of the medicinal product. The importance of the pharmacist's expertise in the administration of a therapy by the feeder tube is evident. Indeed, 40% of medicinal products have to be managed by the pharmacist without any data provided by the manufacturer, research studies, or evidence-based practices present in the literature. The effervescent tablets are the first choice (to be avoided in patients on a low sodium diet or with phenylketonuria) Alternatives: liquid formulation to be diluted with 60 mL of water (contains ethyl alcohol), or Ranitidine 15 mg/mL galenic preparation [8,9]

CYTOTEC 200 (PFIZER) Tablets Yes
Crush the tablet in a mortar, add 15 mL water, draw the suspension into the syringe and administer immediately Rinse the mortar with 15 mL water, draw this water into the syringe and administer Due to the poor stability of the API better an alternative therapy (Ranitidine or Lansoprazole) [      Grind the tablet and suspend the powder in 10 mL water, then administer immediately Stop EN at least 30 min before drug administration Divisible tablet. [10] Glimepiride ( [8,9] [8,9]      Administer the two drugs separately Flush with 10 mL water between each one [8,9] C04AD03 Pentoxifylline (400 mg) TRENTAL (SANOFI)

Coated tablets Yes
The tablet is not easily dispersed in water, due to the coating, but requires gentle stirring for 5 min A fine suspension is obtained which should be administered immediately Better to use capsules [10]     Grind the tablet and dissolve the powder in 10 mL water, then administer immediately Alternative: Entumin drops to be diluted with 50 mL water

SEREPRILE (SANOFI) Tablets Yes
Grind the tablet and dissolve the powder in 10 mL water, then administer immediately Administer at a fixed time

Coated tablets Yes
Grind the tablet and disperse it in 10 mL water, then administer immediately Preferably use drops Incompatible with PVC tubes [10] N06AB05 Paroxetine hydrochloride (20 mg)

Coated tablets Yes
Grind the tablet and disperse the powder in 10 mL water, then administer immediately Rinse the tube well after administration Preferably switch to another selective serotonin reuptake inhibitor FEVARIN (BGP PRODUCTS) N06AB08 Fluvoxamine maleate (50 mg) MAVERAL (BGP PRODUCTS)

LEDERFOLIN (PFIZER) Tablets Yes
Grind the tablet and dissolve the powder in 10 mL water, then administer Alternative: powder for reconstitution for injection [10] V03AF04 Calcium levofolinate (2.5 mg)

LEDERFOLIN (PFIZER)
Granules for oral solution Yes to rinse the tube between one drug and another with at least 5-10 mL of water to ensure that the tube is clean during the transition to the next drug; 7.
rinse the tube with at least 40 mL of water after the administration; 8.
restart the feed, unless a break is required.
A thorough description of the recommendations for each pharmaceutical form is summarized in Table 5. Table 5. General recommendations for medications given by tube.

Pharmaceutical Form Method of Administration
Liquid forms (drops, syrups, suspensions) High osmolar or very viscous liquids must be suitably diluted before being administered If the osmolality is not known, it is advisable to dilute the drug with at least 30 mL of water to make it compatible with gastric administration and to prevent diarrheal phenomena from osmotic effect Shake and mix the solution or suspension well Administer directly by tube

Tablets Chewable tablets
The tablets must be crushed in the crusher until they are reduced to a fine and homogeneous powder to promote better absorption and avoid obstruction of the tube Transfer the powder to a plastic cup Effervescent tablets Put the tablet directly in a plastic cup Dispersible/soluble tablets Put the tablet directly in a plastic cup

Capsules
Open the capsule and insert the powder in a plastic cup, verifying the content first Soft capsules They cannot be administered Modified-release tablets/capsules Gastroresistant tablets, enteric-coated tablets Sublingual tablets

Conclusions
The present paper has highlighted the need to oversee and investigate the problem of administering drugs by feeding tube in dysphagic patients. The management of therapeutic pathways, due to the complexity and high clinical risk that it entails, requires advanced, updated, and integrated skills. The alteration of oral pharmaceutical forms, if not properly managed, can lead to errors in therapy, side effects, occupational exposure by inhalation or contact with the drug, and cost increase. The advice of the clinical pharmacist, especially for the verification of alternative pharmaceutical forms, can prove effective in reducing therapeutic errors. This study provides health-care teams a practical guide for the correct administration of oral drugs in patients undergoing EN through PEG. The hope that has accompanied the drafting of this document is that it can be a tool that allows the prescriber to receive the correct information on the drug and consequently to adapt the pharmacological prescription for the new type of administration. Secondly, we want to provide nurses with practical suggestions regarding the correct methods of handling and adequate administration of drugs via tube, in order to ensure continuity of care and adherence to the therapeutic program.