Farmacia HOSPITALARIA

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Farmacia

HOSPITALARIA

www.elsevier.es/ farmhosp

Farmacia HOSPITALARIAVolumen 32. Número 6. Noviembre / Diciembre 2008

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ÓRGANO OFICIAL DE EXPRESIÓN CIENTÍFICA DE LA SOCIEDAD ESPAÑOLA DE FARMACIA HOSPITALARIA Editorial

Líneas estratégicas de formación en la Sociedad Española de Farmacia Hospitalaria (SEFH) M.Á. Calleja Hernández Originales

Morbilidad y costes asociados al síndrome depresivo en sujetos con ictus en un ámbito poblacional

A. Sicras Mainar, R. Navarro Artieda, M. Blanca Tamayo, J. Rejas Gutiérrez y J. Fernández de Bobadilla Calidad de la farmacoterapia y seguridad de los pacientes en hemodiálisis tratados con estimulantes eritropoyéticos T. de Diego Santos, M. Climente Martí, E.V. Albert Balaguer y N.V. Jiménez Torres CONSULTENOS: programa de información al alta hospitalaria. Desarrollo y resultados del primer año de funcionamiento en 5 hospitales M.Á. Pardo López, M.T. Aznar Saliente y E. Soler Company Psicofármacos y gasto en la prisión de Madrid III (Valdemoro) I. Algora-Donoso y O. Varela-González Originales breves

Síndrome tóxico del segmento anterior: investigación de un brote M. Sarobe Carricas, G. Segrelles Bellmunt, L. Jiménez Lasanta y A. Iruin Sanz Estabilidad en suero fisiológico del busulfán intravenoso en un envase de poliolefinas J. Nebot Martínez, M. Alós Albiñana y O. Díez Sales Artículo especial

Mejorar la adherencia al tratamiento antirretroviral.

Recomendaciones de la SPNS/SEFH/GESIDA Cartas al Director

Lenalidomida: efectos adversos y comercialización L. Ortega Valín, J.J. del Pozo Ruiz, C. Rodríguez Lage y F. Ramos Ortega Revisión del tratamiento con gemtuzumab ozogamicin a propósito de 3 casos clínicos E. Fernández Cañabate, M. Longoni Merino, C. Estany Raluy y R. Pla Poblador Formulación de glicopirrolato tópico en hiperhidrosis R. Albornoz López, R. Arias Rico, V. Torres Degayón y A. Gago Sánchez

www.elsevier.es/farmhosp

Abstract

Obj ect ive: To design a programme for pharmaceut ical care for t he elderly wit h renal failure in 3 nursing homes in t he region of Valencia.

Met hod: A 9-mont h long, prospect ive st udy int o pharmaceut ical int ervent ions was carried out . The st udy assessed t he development of renal f unct ion and t he ef f ect iveness of drug dosage adj ust ment wit h pharmacokinet ics affect ed by renal failure in pat ient s wit h creat inine clearance below 30 mL/ min.

Resul t s: Fift y-t wo resident s of 251 cent res present ed creat inine clearance lower t han 30 mL/

min. Fort y-seven out of 74 pharmaceut ical int ervent ions were accept ed. The drugs which were mainly used were: diuret ics, ant ibiot ics, ant i-inf lammat ories, ant iemet ics, and ranit idine.

Alt hough t he process of renal disease cont inued it s course, in most cases t he follow-up paramet ers of effect iveness and safet y (in t erms of renal t oxicit y) were maint ained wit hin t he est ablished limit s.

Conclusion: The int ervent ions carried out showed, in most cases, t o be safe (renal t oxicit y) and effect ive, wit h some except ions which required more individual follow-up.

Ajuste de dosiicación de medicamentos en pacientes ancianos institucionalizados con insuiciencia renal

Resumen

Objetivo: Describir un programa de atención farmacéutica en ancianos con insuiciencia renal en 3 cent ros sociosanit arios de la Comunidad Valenciana.

KEYWORDS

Chronic renal failure;

Pharmaceut ical care;

Nursing homes;

Geriat rics

PALABRAS CLAVE Insuiciencia renal crónica;

At ención farmacéut ica;

*Corresponding aut hor.

E-mail address: mont anyes_bel@gva.es (B. Mont añés Pauls).

BRIEF REPORT

Adjusting the dosage of medication in institutionalised elderly patients with renal failure

B. Montañés-Pauls,

^a,

* C. Sáez-Lleó,

^a

and G. Martínez-Romero

^b

aServicio de Farmacia, Cent ro Sociosanit ario El Pinar, Cast ellón, Spain

aServicio de Farmacia, Cent ro Sociosanit ario La Cañada, Valencia, Spain

Received April 7, 2008; accept ed Sept ember 15, 2008

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Introduction

One of t he most commonly report ed and predict able changes associat ed wit h ageing is decreased renal funct ion.

Mild chronic renal failure (CRF) (glomerular iltration [GF>40 mL/ min) is generally asympt omat ic, but when t he GF is

<30-40 mL/ min, import ant disorders begin t o appear.¹ One of the consequences is that it is more dificult to eliminat e many drugs, especially t hose excret ed renally.

A populat ion st udy in t he Unit ed St at us which obt ained dat a from 15625 non-inst it ut ionalised adult pat ient s est imat ed t hat CRF wit h a GF<60 mL/ min has a prevalence of 4.6%. One not ewort hy aspect is t he associat ion bet ween advanced age and an increased prevalence of GF<60 mL/ min.² It is ext remely import ant t o design early CRF det ect ion st rat egies, keeping in mind t he fact ors involved in CRF’s evolut ion, including pharmacological t reat ment . Therefore, in pat ient s wit h an alt ered renal funct ion who are on mult iple medicat ions, nephrot oxic drugs should be avoided and dosages adj ust ed accordingly.³

This art icle describes a pharmaceut ical assist ance programme for elderly CRF pat ient s which evaluat es t he effect iveness and change in renal funct ion for each pharmaceut ical int ervent ion administ ered.

Method

Prospect ive st udy over 9 mont hs (April-December 2006).

An act ion programme was designed t o ident ify drugs t hat should be subst it ut ed and/ or have t heir dosages adj ust ed in elderly CRF pat ient s. The programme has been implement ed in t hree healt h cent res. It includes 251 resident s (69.7%

women), wit h an average age of 81.6 years.

When t he resident is admit t ed t o t he healt h cent re, his/

her medicat ions are recorded along wit h ant hropomet ric st at ist ics, clinical diagnoses, et c. He/ she schedules an analysis t o record serum creat inine (Crser) and calculat es creat inine clearance (Clcr) using t he Cockroft -Gault equat ion.⁴

Men: Clcr = (140 – age) × weight / 72 + (Crser)

Women: Clcr = (140 – age) × weight / 72 + (Crser) × 0.85

Mét odo: Est udio prospect ivo de 9 meses de las int ervenciones farmacéut icas realizadas, para evaluar la evolución de la función renal y la efect ividad del aj ust e posológico de fármacos con farmacocinética afectada por insui ciencia renal en pacientes con aclaramiento de creatinina inferior a 30 ml/ min.

Result ados: Cincuent a y dos resident es de los 251 valorados present aron aclaramient o de crea- t inina inferior a 30 ml/ min. De las 74 int ervenciones farmacéut icas realizadas, se acept aron 47.

Los fármacos mayormente implicados fueron: diuréticos, antibióticos, antiinlamatorios, antie- mét icos y ranit idina. Aunque el progreso de la enfermedad renal sigue su curso, en la mayoría de los casos los parámet ros de seguimient o de la ef ect ividad y la seguridad (en t érminos de t oxicidad renal) se mant ienen dent ro de los límit es est ablecidos.

Conclusión: Las int ervenciones realizadas se muest ran en la mayoría de los casos seguras (t oxicidad renal) y efect ivas, con alguna excepción, que requiere un seguimient o más individualizado.

Geriat ría

In pat ient s wit h grade III obesit y, t he weight -adj ust ed dose is calculat ed as follows⁵:

WD = W_ideal + 0.4 (W_current — W_ideal)

W_ideal men: 56.2 + 0.555 (height [cm] — 152.4)

W_ideal women: 53.1 + 0.535 (height [cm] — 152.4)

Once Clcr has been calculat ed, we consider values below 30 ml/ min, since most elderly pat ient s present Clcr below 50 ml/min. Once an episode or CRF has been identiied, eit her when regist ering at t he cent re or when modifying t reat ment , t he pat ient becomes part of t he programme. A dosage adj ust ment programme was designed based on an exhaust ive bibliographic st udy,^6-9 and an alert syst em was set up on a comput er programme (Sinphos^®, Grifols). We performed follow-up on t he pharmaceut ical int ervent ions prescribed by t he doct or. There was no follow-up for drugs t hat required a dosage adj ust ment for a short -t erm, non- nephrot oxic t reat ment .

Nephrotoxic drugs

Follow-up on renal funct ion using serum urea values and GF at t ime of int ervent ion and at six mont hs: bet a- lactams, quinolones, non-steroidal anti-inlammatories, and angiot ensin convert er enzyme inhibit ors.

Drugs requiring a dosage adjustment for long-term treatment

1. Diuret ics and ant i-hypert ensive drugs: follow-up on blood pressure (BP) at t ime of int ervent ion, at 1 week, 1 mont h, and 3 mont hs. Crit erion for high BP: values above 140/ 90 mmHg (stage 1 arterial hypertension [AH],¹⁰ or cases in which a pat ient in st age 1 passes t o st age 2 (AH>160/100 mmHg).

2. Alopurinol: follow-up on uric acid values at t he t ime of int ervent ion and at 6 mont hs. Crit erion for uric acid increase: values above 7 mg/ dL (reference laborat ory [RL]).

3. Ant i-diabet ic drugs: follow-up on glucose values at t he t ime of int ervent ion and at 6 mont hs. Crit erion for high

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glycaemia: values above 120 mg/ dL (RL). Drug dosage adj ust ment s in elderly inst it ut ionalised pat ient s wit h renal failure.

4. Digoxin and ant i-epilept ics: follow-up on plasma values at t ime of int ervent ion, at 1 mont h and at 6 mont hs.

Evaluating renal function

1. GF is calculat ed based on Clcr and uses as a reference the classiication scheme proposed by the Spanish Societ y of Nephrology (SEN)¹¹ (Table 1). Given t hat most of our pat ient s are in st age 2 or above, a change in renal funct ion st age is considered t o indicat e a worsening condit ion.

2. Urea: worsening is indicat ed by values above 50 mg/ dL (RL).

Results

Out of t he t ot al of 251 pat ient s t hat were evaluat ed, 52 (20.7%) of t he elderly resident s present ed CRF (Clcr<30 mL/ min).

Sevent y-four pharmaceut ical int ervent ions t ook place, and 47 were accept ed. These included 7 changes in t reat ment , 37 dosage adj ust ment s, and 3 cases of discont inuing t he t reat ment . The index of accept ance by t he medical st aff was 63.5%.

Table 2 shows t he most frequent ly involved medicat ions.

Table 3 present s analyt ic dat a and blood pressure recorded during follow-up on t he int ervent ion.

Of t he 47 int ervent ions t hat were performed, long-t erm follow-up (at least 6 mont hs) could be carried out for 33;

t he rest of t he int ervent ions only involved a t reat ment modiication during a brief time.

We evaluat ed t reat ment safet y for t hose 33 int ervent ions wit h follow-up according t o whet her or not renal funct ion decreased (Table 1). There was a change in renal funct ion st age in 5 int ervent ions (2 in t he same pat ient ). If we observe urea values, we see t hat 18 show values above 50 mg/ dL at 6 mont hs from t he int ervent ion, alt hough in 15 t hese values were already above 50 mg/ dL at t he t ime

of int ervent ion, and t he rest remained const ant or even decreased (10 int ervent ions).

Regarding t he effect iveness of t he t reat ment , we can use t he abovement ioned paramet ers from t he 14 cases in which effect iveness can be evaluat ed obj ect ively t o show t hat t he t reat ment was effect ive in 12 cases.

Discussion

Dat a obt ained from t he Kidney Disease Regist ry at t he SEN corroborat es t hat Spain has one of t he highest CRF rat es among European count ries, and t hat t he magnit ude of t he problem, which is linked t o t he ageing populat ion, could increase in t he near fut ure.

Table 1 Spanish Nephrology Society’s proposed classiication of different renal function stages according to glomerular iltration (GF) and associated renal damage

St age Descript ion GF, mL/ min Renal damage

Normal Increased risk >90 with CKD risk

fact ors

Table 2 Drugs most frequently involved in interventions for medicat ion-relat ed problems in inst it ut ionalised elderly pat ient s wit h renal failure

Treat ment group No. of int ervent ions

Diuret ics 15

Ant ibiot ics 12

Ranit idine 6

Anti-inlammatories 6

Ant ihemet ics 6

Pot assium 5

Alopurinol 4

Ant ihypert ensives 4

Ant ihist amines 4

Ant idepressant s 3

Digoxin 3

Memant ine 2

Alendronat 1

Analgesics 1

Ant idiabet ics 1

Ant iepilept ics 1

1 Renal damage with normal or high GF >90 Albuminuria, proteinuria, haematuria 2 Renal damage wit h normal or low GF 60-89 Albuminuria, prot einuria, haemat uria 3 Renal damage wit h normal or low GF 30-59 Chronic renal failure

Early renal failure

4 Severely diminished GF 15-29 Chronic renal failure

Advanced renal failure Terminal pre-CKD

5 Renal failure <15 (or dialysis) Renal failure, uraemia, t erminal kidney disease

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Table 3 Follow-up on pharmaceutical interventions for medication-related problems in institutionalised elderly patients with kidney failur

Int ervent ion GF1, GF2, Urea1, Urea2, BPbefore, BPweek, BPmont h, BP3 mont hs,

mL/ min mL/ min mg/ dL mg/ dL mm Hg mm Hg mm Hg mm Hg

Int ervent ions in diuret ic t reat ment s. Proposal: replace hydrochlorot hiazide and/ or spironolact one wit h ASA diuret ics

1 45 42 51 52 140/ 80 155/ 80 140/ 80 140/ 80

2 36.3 59 113 39 130/ 80 120/ 65 120/ 70 120/ 70

3 27.3 24.6 80 76 150/ 50 110/ 56 150/ 80 160/ 80

4 48 48 22 21 150/ 90 150/ 80 109/ 60 140/ 70

5 42.4 41.5 65 80 100/50 − − 100/60

Int ervent ions in ant ihypert ensive t reat ment . Proposal: dosage adj ust ment

1 34.1 25.4 97 305 130/ 70 100/ 35 130/ 70 115/ 75

2 46.9 54.8 91 66 130/ 60 110/ 50 120/ 60 100/ 60

Itervention GF1, mL/ min GF2, mL/ min Urea1, mg/ dL Urea2, mg/ dL Uric1, mg/ dL Uric2, mg/ dL Int ervent ions in alopurinol t reat ment . Proposal: dosage adj ust ment

1 34.1 25.4 97 305 4.5 6.3

2 36.3 59 113 39 3.2 8

3 36.3 47.1 69 65 10.6 6.7

Intervention GF1, mL/ min GF2, mL/ min Urea1, mg/ dL Urea2, mg/ dL

Int ervent ions in NSAIDs t reat ment s. Proposal: replace wit h paracet amol or opioids

1 45 42 51 52

2 38.4 42.2 51 52

3 35.6 30.3 143 110

Int ervent ions in t reat ment wit h ranit idine. Proposal: dosage adj ust ment

1 49.5 49.5 113 39

2 63.7 64.5 51 48

3 27.3 24.6 80 76

4 51.4 51.4 52 28

5 51.4 60 94 74

Int ervent ions in t reat ment wit h ant ibiot ics. Proposal: dosage adj ust ment

1 64.5 64 48 59

2 32.7 22.7 136 233

3 30.4 18.7 52.6 32.4

4 51.4 51.4 52 28

5 41.9 41.3 86 78

6 47 46.7 34 33

7 46.2 51.4 43 36

Int ervent ions in t reat ment wit h met oclopramide. Proposal: dosage adj ust ment

1 51.9 50.6 32 51

Int ervent ions in t reat ment wit h ant idepressant s. Proposal: dosage adj ust ment

1 51.9 50.6 32 51

2 41.9 41.3 86 78

3 53 51.9 34 33

Intervention GF1, mL/ min GF2, mL/ min Urea1, mg/ dL Urea2, mg/ dL Level1 Level2

Int ervent ions in t reat ment wit h digoxin (µg/ mL): Proposal: dosage adj ust ment

1 36.3 59 113 39 0.7 0.8

2 51.4 51.4 52 28 1.2 1.6

3 45.7 45.7 41 49 0.6 1

Int ervent ion GF1, GF2, Urea1, Urea2, Glucose1, Glucose²,

mL/ min mL/ min mg/ dL mg/ dL mg/ dL mg/ dL

Int ervent ions in t reat ment wit h ant idiabet ics. Proposal: replace wit h a different sulphonylurea drug

1 34.9 35.1 32 35 110 83

1 indicates before intervention; 2, six months after intervention; BP, blood pressure; GF, glomerular iltration; NSAIDs, non-steroidal anti-inlammatory drugs.

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One of t he fundament al aspect s in t he follow-up of pharmaceut ical t reat ment in elderly pat ient s is evaluat ing whet her t hat t reat ment is consist ent wit h t he dosage and/

or guidelines indicat ed by t he pat ient ’s Clcr. Aft er carrying out t he int ervent ion, it is appropriat e t o follow up on bot h t he safet y and t he effect iveness of t his t reat ment .

Wit hin t his cont ext , if we analyse t he dat a obt ained from our st udy, we see t hat approximat ely 21% of all pat ient s have a Clcr below 30 mL/ min, which is similar t o ot her percent ages described in t he bibilography.^1-3,12,13

As f or t he index of accept ance by t he medical st af f , we see t hat t he result ing value is not very high^14-16; t his may be due t o t he f act t hat most of t he proposed int ervent ions were adj ust ment s t o t he dosage, which could lead t o dist rust f or t he t reat ment ’s ef f ect iveness on t he part of st af f members. Consequent ly, we are considering doing f ollow-up on t he int ervent ions t hat were accept ed and carried out in order t o evaluat e bot h t heir ef f ect iveness and t he evolut ion of renal f unct ion in t he case of t reat ment s that were modiied.

Upon evaluat ing t he evolut ion of renal funct ion wit h each t reat ment , t he result s indicat e t hat renal funct ion in these patients is already signiicantly impaired, and t hat t he kidney disease cont inues t o progress despit e t he pharmaceut ical t reat ment s administ ered.

Regarding t he effect iveness of t hese t reat ment s, and t aking t he direct ives of t he Joint Nat ional Commit t ee¹⁰ int o considerat ion, we observe t hat where t here were int ervent ions in diuret ic and ant i-hypert ensive t reat ment s, all pat ient s maint ained BP values below t he set limit s at 6 mont hs, even when BP was above t he limit at t he t ime of int ervent ion, except in 1 case in which t he syst olic pressure was above 140 mm Hg. Furt hermore, for int ervent ions in digoxin and oral ant i-diabet ic drug t reat ment s, we see that pharmacokinetic values (in the irst case) and fast ing glucose levels (in t he second) remained wit hin t he est ablished limit s.

Three int ervent ions were made in alopurinol t reat ment ; in 2 cases, uric acid values at 6 mont hs were lower t han 7 mg/ dL and in t he ot her it was higher t han t hat amount .

Therefore, we can conclude t hat t he maj orit y of t he int ervent ions t he pharmaceut ical specialist carried out t o modify t reat ment s so as not t o exacerbat e renal failure seem t o be safe and effect ive where renal funct ion is concerned;

however, t here are except ions in which it is appropriat e t o re-adj ust t he dosage and/ or guidelines t o obt ain t he desired result s. For t his reason, it is recommended t hat a mult i-disciplinary t eam carry out an individual follow-up of reference values (pressure, analysis).

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