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Inicio Farmacia Hospitalaria (English Edition) Thermolabile Drugs. Operating Procedure in the Event of Cold Chain Failure
Journal Information
Vol. 35. Issue 4.
Pages 190.e1-190.e28 (July - August 2011)
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13725
Vol. 35. Issue 4.
Pages 190.e1-190.e28 (July - August 2011)
Brief Report
DOI: 10.1016/j.farmae.2010.07.001
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Thermolabile Drugs. Operating Procedure in the Event of Cold Chain Failure
Medicamentos termolábiles. Protocolo de actuación en la rotura de la cadena de frío
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13725
L. Periáñez Parraga??
Corresponding author
leonord.perianez@ssib.es

Corresponding author.
, A. Gómez-Lobón, I. Gamón Runnenberg, R. Seco Melantuche, O. Delgado Sánchez, F. Puigventós Latorre
Servicio de Farmacia, Hospital Universitario Son Dureta, Palma de Mallorca, Mallorca, Spain
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Figures (1)
Tables (2)
Table 1. Classification of Drugs.
Table 2. Recommendations After Breaking the Cold Chain.
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Abstract
Objective

To establish a standard operating procedure in the event of cold chain failure.

Method

We selected thermolabile drugs included in the hospital's pharmaceutical guide. We performed a review of the available literature, classifying each drug into a given category with an intervention protocol for each one.

Results

We reviewed 254 drugs (162 active ingredients). Categories were: A (stable ≥28days at 25°C): 65 drugs; B (≥7days at 25°C): 47 drugs; C (≥48h at 25°C): 30 drugs; D (<48h at 25°C): 47 drugs; E (unstable >8°C): 12 drugs; F (batch-dependent) 22 drugs. Thirty-one drugs were not classified into any category.

The intervention protocol consisted of establishing a system to monitor the products concerned, and discarding or returning them to the laboratory if they were to exceed the time or temperature limit indicated for each category.

Discussion

The aim of this study is to make intervention quicker in the event of cold chain failure.

Keywords:
Drug stability
Drug storage
Refrigeration
Cold chain
Resumen
Objetivo

Establecer un procedimiento normalizado de trabajo en caso de rotura de cadena de frío.

Método

Se seleccionaron los medicamentos termolábiles incluidos en la guía farmacoterapéutica del hospital y se revisó la bibliografía disponible, clasificándolos en categorías con un protocolo de actuación en cada caso.

Resultados

Se revisaron 254 medicamentos (162 principios activos). La distribución por categorías fue: A (estable ≥28 días a 25°C): 65 medicamentos; B (≥7días a 25°C): 47; C (≥48h a 25°C): 30; D (<48h a 25°C): 47; E (no estable >8°C): 12; F (depende del lote): 22. No se clasificaron en ninguna categoría 31 medicamentos.

El protocolo de actuación consistió en establecer un sistema de seguimiento de los medicamentos afectados y desechar o devolver al laboratorio en caso de superarse el límite de tiempo o temperatura establecido en cada categoría.

Discusión

El trabajo realizado pretende facilitar la rápida actuación en aquellas situaciones de rotura de la cadena de frío.

Palabras clave:
Estabilidad
Conservación de fármacos
Refrigeración
Cadena de frío
Full Text
Introduction

The cold chain is the set of logistical links that guarantee that a temperature between 2°C and 8°C is maintained during the processes of storage, handling, transport and distribution of drugs. If this is not done, drug properties are liable to change in varying degrees, depending on the temperature reached and the time spent at that temperature.

There are procedures for receiving, storing and distributing drugs in hospitals to ensure that the cold chain is maintained. Standard operating procedures and facilities ensure that the proper temperature is maintained. The complexity of drug distribution processes in hospitals means that there are cold storage facilities available in a large number of locations in the pharmacy department storage areas, as well as the drug storage areas of inpatient units, day hospitals, operating rooms and outpatient clinics, among others.

The cold chain may be broken in many unexpected ways during daily practice (e.g., due to a power failure, cold room breakdowns, inadequate transportation or an error in storage conditions). These incidents may affect just a few units of a drug in a hospital ward or may affect complete clinical containers due to a refrigerator failure.

Administering a drug which has been inadequately stored can have highly variable potential consequences for the patient. Some medications are affected by a temporary and an isolated break in the cold chain: a number of drugs may lose some efficacy of little clinical relevance, while others may have a total loss of activity or may even become toxic.1

In addition, a break in the cold chain may have a significant economic impact for the hospital if the full activity of a drug cannot be guaranteed and it has to be disposed of, and there were no conditions established for its return to the pharmaceutical company supplying it.

The potential clinical and economic impacts posed by the loss of this group of drugs make it necessary to have a protocol for maintaining the cold chain and establishing actions if it is broken. This includes a drug stability report, including the time and temperature to which the drug has been exposed. It is also important to provide information about any such event, as affected batches will have to be withdrawn, and it is important to know whether they can be used or not.

The aim of this study was to establish a standard procedure for a break in the cold chain, prepare an updated list (to 2010) on the maximum stability of thermolabile active ingredients at room temperature, classify them according to the possibility of re-using them for certain time periods and provide a communication system on the hospital intranet and via the Internet.

Method

The main active ingredients to be kept at a temperature between 2°C and 8°C or in the freezer were selected from the hospital pharmacotherapeutic guide.

A review of previously published studies in PubMed with the MESH Drug Stability, Drug storage, refrigeration and Cold chain was carried out.2–10 The information available from the summaries of product characteristics (SmPCs) was taken and the pharmaceutical manufacturer was consulted by fax or e-mail if there was any doubt or lack of data.

An Excel table was prepared, which included speciality-specific data, bibliographic references, and the contact details of the pharmaceutical company department, where appropriate.

Finally, agreement was reached within the pharmacy department on a standard operating procedure (SOP) for any break in the cold chain, which sorted the drugs into 6 categories based on the time they were stable outside of the refrigerator (Table 1).

Table 1.

Classification of Drugs.

Category  Stability  Action 
Stable ≥28 days at 25°C  Label if it meets the conditions. If not, discard 
Stable ≥7 days and <28 days at 25°C  Label if it meets the conditions. If not, discard 
Stable ≥48h and <7 days at 25°C  Label if it meets the conditions. If not, discard 
Stable <48h at 25°C  Evaluate individually depending on the time and temperature reached 
Not stable outside the fridge (>8°C)  Discard 
Stability depends on the batch  Consult laboratory 
Results

A total of 254 medicinal products corresponding to 162 active ingredients were reviewed (Table 2).

Table 2.

Recommendations After Breaking the Cold Chain.

Active Ingredient  Drug Product  Manufacturing Laboratory  Stability at Room Temperature (22–25°C)  Reference  Contact Telephone No.  Category 
Abciximab  Reopro® vial 50mg/ml  Lilly  8 days at 28°C (192h)  Consult lab 28/07/09  916635000 
Carglumic acid  Carbaglú® 200mg tablets  Orphan Europe  1 month at <30°C  SmPCs (2003)   
Adalimumab  Humira ® 40mg prefilled syringe  Abbott Laboratories  8Cobos Campos et al., 20063   
Agalsidase alfa  Replagal® 3.5mg vial  Shire Human Genetic Therapies  24SmPCs (2006)   
Alemtuzumab  MabCampath® 30mg vial  Bayer Healthcare  7 days at 25°C  Consult lab 20/2/09  934956500 
Alfacalcidol  Etalpha® ampoules 1mcg  Leo Pharma  1 year at 25°C  Bovaira García et al., 20044  932213366 
Alfacalcidol  Etalpha® ampoules 2mcg  Leo Pharma  1 year at 25°C  Bovaira García et al., 20044  932213366 
Alfacalcidol  Etalpha® drops  Leo Pharma  1 year  Consult lab 16/02/09, Bovaira García et al., 20044  932213366 
Alprostadil  Alprostadil® 500mcg/ml  Pfizer  4 months  Cuervas-Mons et al., 2004,6 García Vázquez et al., 19977   
Alteplase  Actilyse® 20mg  Boehringer Ingelheim Spain  3 years at <25°C  Bovaira García et al., 20044   
Alteplase  Actilyse® 50mg  Boehringer Ingelheim Spain  3 years at <25°C  Bovaira García et al., 2004,4 Cuervas-Mons et al., 20046   
Amphotericin BAbelcet® 50mg vial  Cephalon Pharma  1 day outside fridge=9 days in fridge (change expiry date)  Cobos Campos et al., 20063  Specific recommendation   
      Cuervas-Mons et al., 20046     
Amphotericin B  Fungizona® 50mg vial  Bristol Myers Squibb  2 weeks-1 month  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Digoxin antidote  Digitalis Antidot® 80mg vial  Roche Farma Farma  20 days up to 40°C  Silgado et al., 20062   
Asparaginase  Erwinase® (ME) 10,000IU vial  Opi  2 years  García Vázquez et al., 19977   
AsparaginaseKidrolase® 10,000IU vial  Opi  48h (1), 7 days (2)  Cuervas-Mons et al., 20046 (1)     
    García Vázquez et al., 19977 (2)     
Atosiban  Tractocile® 37.5  Ferring  24h at 25°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Atosiban  Tractocile® 6.75  Ferring  24h at 25°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Atracurium  Atracurio® 25mg amp.  Inibsa  1 month 30°C (loss of 8%)  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Basiliximab  Simulect® 20mg vial  Novartis Farmaceutica  4 days at <25°C  Cuervas-Mons et al., 20046   
BevacizumabAvastin® 100mg vial  Roche Farma  9h at 30°C; 5 days at 15°C  Consult lab 20/2/09  913248100 
Avastin® 400mg vial  Roche Farma  9h at 30°C; 5 days at 15°C  Consult lab 20/2/09  913248100 
BH4  Tetrahydrobiopterin® 10mg  Schircks Laboratories  ≤−20°C: 36 months//≤−10°C: 18 months//≤+5°C: 4 months//>6 months at 25°C: maintains >99.5% activity (although may turn yellow or break more easily)//20–30°C: expires in 2 months//Can be re-frozen  SmPCs (review year not available)   
BH4  Tetrahydrobiopterin® 50mg  Schircks Laboratories  ≤−20°C: 36 months//≤−10°C: 18 months//≤+5°C: 4 months//>6 months at 25°C: maintains >99.5% activity (although may turn yellow or break more easily)//20–30°C: expires in 2 months//Can be re-frozen  SmPCs (review year not available)   
Bleomycin  Bleomicina® 15IU vial  Almirall  28 days  Cobos Campos et al., 2006,3 Sala et al., 2004,5 Cuervas-Mons et al., 2004,6 Silgado et al., 20062   
Busulphan  Busilvex® 60mg vial  Pierre Fabre Iberica  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 20/02/09  934833000 
Calcitonin  Calcitonina Hubber® inject. 100IU  Valeant Pharmaceuticals Iberica  1 month  Cobos Campos et al., 20063   
Calcitonin  Calcitonina Hubber® nasal 200IU  Valeant Pharmaceuticals Iberica  1 month  Cobos Campos et al., 20063   
Carboprost  Hemabate® 250  Zlb Behring  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 20/02/09  933068117 
Carmustine  BiCNU® (ME) 100mg vial  Bms  The appearance of droplets indicates that the product is not fit to be used  Cobos Campos et al., 20063   
Caspofungin  Cancidas® 50mg  Merck Sharp Dohme  48Cobos Campos et al., 2006,3 Sala et al., 2004,5 Cuervas-Mons et al., 2004,6 Silgado et al., 20062   
Caspofungin  Cancidas® 70mg  Merck Sharp Dohme  48Cobos Campos et al., 2006,3 Sala et al., 2004,5 Cuervas-Mons et al., 2004,6 Silgado et al., 20062   
Cefonizid  Monocyd® 1g IM/IV  Rottapharm  18 months  Silgado et al., 2006,2 Cuervas-Mons et al., 20046   
Cetuximab  Erbitux® 100mg vial  Merck Sharp Dohme  20Bovaira García et al., 20044   
Cisatracurium  Nimbex® 10mcg/ml  Glaxo SmithKline  1 month at 25°C: 5% degradation 1 day outside fridge=10 days in fridge  Cobos Campos et al., 2006,3 Sala et al., 20045    Specific recommendation 
Cisatracurium  Nimbex® 2mcg/ml  Glaxo SmithKline  1 month at 25°C: 5% degradation 1 day outside fridge=10 days in fridge  Cobos Campos et al., 2006,3 Sala et al., 20045    Specific recommendation 
Liposomal cytarabine  Depocyte® 50mg vial  Mundi Pharma Pharmaceuticals  72h at 25°C  Consult lab 20/02/09  913821870 
Chlorambucil  Leukeran® 2mg tablets  Glaxo SmithKline  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 22/12/09  918070301 
Chloramphenicol  Colircusi cloranfenicol®  Alcon Cusi  Storage: 15 days at 25°COnce open: 1 month  Bovaira García et al., 2004,4 Silgado et al., 20062   
Chloramphenicol  Colircusi de Icol®  Alcon Cusi  Storage: 15 days at 25°COnce open: 1 month  Bovaira García et al., 20044   
Anti-inhibitor coagulant complex  Feiba® 4 1000UF  Baxter  6 months  Sala et al., 20045   
Daclizumab  Zenapax® 5mg/ml  Roche Farma  14 days at 25°C, 7 days at 30°C  Bovaira García et al., 2004,4 Silgado et al., 20062   
Daptomycin  Cubicin® 500mg vial  Novartis Farmaceutica  60h at 25°C  Consult lab 16/02/09  933064200 
Denileukin diftitox  Ontak® 300mg/2ml  Ferrer Farma  No information available  Consult lab 20/12/09  936003700 
Desmopressin  Minurin® drops  Ferring  1 month  Cobos Campos et al., 2006,3 Sala et al., 2004,5 Cuervas-Mons et al., 20046   
Desmopressin  Minurin® inject  Ferring  24Cobos Campos et al., 2006,3 Sala et al., 2004,5 Cuervas-Mons et al., 20046   
Dinoprostone  Prepidil® 0.5 gel  Pfizer  1 month  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Dinoprostone  Propess® 10mg  Ferring SAU  <24h at 2–8°C: re-freeze. If thawed completely: 4 weeks at 2–8°C. Room temperature: 24Consult lab 03/08/09   
Dinoprostone  Prostaglandina E2® 10mg/ml  Pfizer  1 month at 25°C  Cobos Campos et al., 20063   
Dopamine hydrochloride  Duodopa gel intestinal cassettes 100ml  Solvay Pharma  4 days at 25°C  Consult lab 05/03/09  934954500 
Dornase alpha  Pulmozyme® 2.5mg amp.  Roche Farma  24h at 30°C (1)2.5 days at 30°C (2)  Cuevas (1), Sala et al., 20045 (1), Silgado et al., 20062 (2), Bovaira García et al., 20044 (2)   
Doxycycline  Vibravenosa® 100mg  Pfizer  1 month  Cobos Campos et al., 20063   
Doxorubicin (=adriamycin)  Doxorrubicina® 50mg vial  Ferrer Farma  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 20/02/09  936003700 
Liposomal doxorubicin  Myocet® 50mg vial  Cephalon Pharma  <1 month  Cobos Campos et al., 2006,3 Silgado et al., 20062   
Pegylated liposomal doxorubicin  Caelyx® 20mg vial  Schering-Plough  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab, Sala et al., 20045   
Drotrecogin  Xigris® 20mg  Lilly  72h up to 28°C  Silgado et al., 20062   
Drotrecogin  Xigris® 5mg  Lilly  72h up to 28°C  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Eculizumab  Soliris® 300mg vial  Alexion Pharma Spain  6–7 days  Consult lab 20/02/09  932723017 
Epirubicin  Farmorubicina® 200mg vial  Pfizer  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 15/02/09   
Eptifibatide  Integrilin® 20mg vial  Glaxo SmithKline  2 months  Cuervas-Mons et al., 20046   
Erythropoietin alpha  Eprex® 40,000IU prefilled syringe  Janssen-Cilag  1h 6Cobos Campos et al., 2006,3 Cuervas-Mons et al., 2004,6 Silgado et al., 2006,2 Bovaira García et al., 20044   
Erythropoietin beta  Neorecormon® prefilled syringe  Roche Farma  3 days  Cuervas-Mons et al., 2004,6 Cobos Campos et al., 2006,3 Silgaro, Sala et al., 20045   
Streptokinase  Streptase® 750,000IU  CSL Behring  Keep at temperature ≤25°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Streptozocin  Zanosar® (ME) 1g vial  Pfizer  Note batch no., expiry, temperature and exposure time and contact laboratory  Cobos Campos et al., 2006,3 Silgado et al., 20062   
Etanercept  Enbrel® 25mg prefilled syringe  Wyeth Farma  24h at ≤25°C; >25°C contact laboratory  Consult lab 21/12/09  913346400 
Etanercept  Enbrel® 25ng/ml paediatric vial  Wyeth Farma  24h at ≤25°C; >25°C contact laboratory  Consult lab 21/12/09  913346400 
Etanercept  Enbrel® 50mg prefilled syringe  Wyeth Farma  24h at ≤25°C; >25°C contact laboratory  Consult lab 21/12/09  913346400 
Factor IX  Factor® IX 600IU  Behring  3 months at 25°C (do not re-refrigerate)  SmPCs (2010)    Specific recommendation 
Factor VIII+Von Willebrand factor  Fanhdi®  Grifols  2 years at 25°C (1)months at 40°C (2)  Cobos Campos et al., 20063 (1), Cuervas-Mons et al., 20046 (2)   
Recombinant Factor VIII  Advate® 1000IU  Baxter  6 months at 25°C (do not re-refrigerate)  SmPCs (review year not available)    Specific recommendation 
Recombinant Factor VIII  Advate® 500IU  Baxter  6 months at 25°C (do not re-refrigerate)  SmPCs (review year not available)    Specific recommendation 
Factor IX plasma  Inmunine® Stim plus 600  Baxter  3 months at 25°C  Sala et al., 20045   
Recombinant Factor IX  Benefix® 500IU  Baxter  1 month at 25°C  Cuervas-Mons et al., 2004,6 Silgado et al., 2006,2 Sala et al., 20045   
Recombinant Factor VIII  Refacto AF® 1000IU vial 4ml  Wyeth Farma  3 months at 25°C. After this time, do not re-refrigerate  SmPCs (review year not available)   
Recombinant Factor VIII  Refacto AF® 250IU vial 4ml  Wyeth Farma  3 months at 25°C. After this time, do not re-refrigerate  SmPCs (review year not available)   
Recombinant Factor VIII  Refacto AF® 500IU vial 4ml  Wyeth Farma  3 months at 25°C. After this time, do not re-refrigerate  SmPCs (review year not available)   
Factor VIIa  Novoseven® 1.2  Novo Nordisk Pharma  24h at 25°C  Silgado et al., 2006,2 Bovaira García et al., 2004,4 Sala et al., 2004,5 Consult lab 18/02/09  913349800 
Factor VIIa  Novoseven® 2.4  Novo Nordisk Pharma  24h at 25°C  Silgado et al., 2006,2 Bovaira García et al., 2004,4 Sala et al., 2004,5 Consult lab 18/02/09  913349800 
Factor VIIa  Novoseven® 4.8  Novo Nordisk Pharma  24h at 25°C  Silgado et al., 2006,2 Bovaira García et al., 2004,4 Sala et al., 2004,5 Consult lab 18/02/09  913349800 
Phenylephrine  Colircusi fenilefrina®  Alcon Cusi  1 month (1)15 days (2)  SmPCs (1), Cobos Campos et al., 20063 (2), Silgado et al., 20062 (2)   
Phentolamine  Regitine®  Novartis Farmaceutica  7 days at 25°C or 2 days at 30°C  Consult lab 21/07/09  933064200 
Fibrin  Tissucol® 2ml  Baxter  48h. Do not re-freeze  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Filgrastim  Neupogen® 300MU  Amgen  7 days, 9–30°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Silgado et al., 2006,2 Sala et al., 20045   
Filgrastim  Neupogen® 480MU  Amgen  7 days, 9–30°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Silgado et al., 2006,2 Sala et al., 20045   
Filgrastim  Neupogen® vials  Amgen  7 days, 9–30°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Silgado et al., 2006,2 Sala et al., 20045   
Fluorescein+oxybuprocaine  Colircusi fluotest®  Alcon Cusi  15 days  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 20044   
Folinic acid  Folinato calcico® 10mg/ml  Ferrer Farma  7–14 days at 25°C  Consult lab 22/12/09  936003700 
Galsulfase  Naglazyme® 5mg vial  Biomarin Europe Ltd  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 22/12/09  620988250 
Antiophidic immunoglobulin  Viperfav®  Sanofi Pasteur MSD  7 days  Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Anti D immunoglobulin 3  Rhopylac® 300mcg syr 2ml  CSL Behring  24h at 25°C  Consult lab 25/08/09  933671870 
Specific immunoglobulin  Gamma Anti D® 1500IU  Grifols  3 months at 25°C, although discarding is recommended  Cobos Campos et al., 20063   
Specific immunoglobulin  Gamma Antihepatitis B 200IU/ml  Grifols  3 months at 25°C, 2 months at 35°C, although discarding is recommended as it is a vaccine  Cobos Campos et al., 20063   
Specific immunoglobulin  Gamma Antitetanos® 500IU  Grifols  12 months at 25°C, 3 months at 35°C, although discarding is recommended as it is a vaccine  Cobos Campos et al., 20063   
Specific immunoglobulin  Imogam® 150IU/ml  Sanofi Pasteur MSD  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 21/12/09  913717800 
Non specific human immunoglobulin  Kiovig® 10Baxter  9 months (do not re-refrigerate)  SmPCs (2006)    Specific recommendation 
Non specific human immunoglobulin  Kiovig® 2.5Baxter  9 months (do not re-refrigerate)  SmPCs (2006)    Specific recommendation 
Non specific human immunoglobulin  Kiovig® 5Baxter  9 months (do not re-refrigerate)  SmPCs (2006)    Specific recommendation 
Non specific human immunoglobulin  Vivaglobin® 160  CSL Behring  3 months or until expiry date if earlier (do not re-refrigerate)  SmPCs (2008)    Specific recommendation 
Gemtuzumab  Mylotarg® 5mg vial  Wyeth Farma  90 days  Sala et al., 20045   
Glatiramer  Copaxone® 20mg prefilled syringe  Sanofi-Aventis  7 days, 15–25°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Silgado et al., 2006,2 Sala et al., 20045   
Gonadotrophin  Gonal F® 300IU 22mcg/0.5ml pref. pen  Serono Spain  3 months  Consult lab 21/12/09  917454400 (Merck) 
Gonadotrophin  Gonal F® 450IU 33mcg/0.75ml pref. pen  Serono Spain  3 months  Consult lab 21/12/09  917454400 (Merck) 
Gonadotrophin  Ovitrelle® 250mcg prefilled syringe  Serono Spain  30 days  Consult lab 21/12/09  917454400 
Gonadotrophin  Puregon® 300IU cassette 0.36ml  Organon Spain  3 months at <25°C, once open 1 month  Consult lab 05/03/09  915673000 
Gonadotrophin  Puregon® 600IU cassette 0.72ml  Organon Spain  3 months at <25°C, once open 1 month  Consult lab 05/03/09  915673000 
Gonadotrophin  Puregon® 900IU cassette 1.08ml  Organon Spain  3 months at <25°C, once open 1 month  Consult lab 05/03/09  915673000 
Hyaluronate  Healon® “5” 23mg/ml prefilled syringe  Panalab  30 days 25°C  Cobos Campos et al., 20063   
Hemin  Normosang® 250mg vial  Orphan Europe  1 week up to 26°C  Silgado et al., 2006,2 Bovaira García et al., 2004,4 Sala et al., 20045   
Infliximab  Remicade® 100 vial  Schering Plough  12 months  Cobos Campos et al., 20063   
C1 esterase inhibitor  Berinert® 500IU vial  Csl Behring  Stable, can be stored at temps up to 25°C  SmPCs (review year not available)   
Insulin  Insuman infusat® 100Sanofi-Aventis  Storage: no information available Once in use: 4 weeks  Consult lab 21/12/09  934859400  Specific recommendation 
Insulin glargine  Lantus® 100U/ml solostar  Sanofi-Aventis  4 weeks at <30°C (including usage time)  Bovaira García et al., 20044   
Insulin aspart  Novorapid flexpen® 100U/ml pens  Novo Nordisk Pharma  Storage: 24h at 25°C. Once in use: 4 weeks  Bovaira García et al., 20044   
Insulin aspart-protamine  Novomix 30 flexpen® 100U/ml pref. pens  Novo Nordisk Pharma  Storage: 24h at 25°C. Once in use: 4 weeks  Bovaira García et al., 20044   
Insulin detemir  Levemir® 100U/ml  Novo Nordisk Pharma  Once in use: 6 weeks (do not re-refrigerate once open or if carried as a spare)  SmPCs (review year not available)    Specific recommendation 
Insulin glulisine  Apidra® 100U/ml solostar  Sanofi-Aventis  4 weeks (including administration time)  SmPCs (review year not available)    Specific recommendation 
Insulin regular  Actrapid® 100IU/ml vial  Novo Nordisk Pharma  Storage: 24h at 9–25°C Once in use: 6 weeks  Cobos Campos et al., 2006,3 Consult lab 25/08/09  913349800 
Insulin regular  Actrapid innolet® 100IU/ml pref. pen  Novo Nordisk Pharma  Storage: 24h at 9–25°C Once in use: 4 weeks  Cobos Campos et al., 2006,3 Consult lab 25/08/09  913349800 
Insulin protamine  Insulatard® 100IU/ml vial  Novo Nordisk Pharma  Storage: 24h at 9–25°C. Once in use: 4 weeks  Cobos Campos et al., 20063   
Insulin protamine  Insulatard flexpen® 100IU/ml pref. pen  Novo Nordisk Pharma       
Insulin protamine  Insulatard innolet® 100IU/ml  Novo Nordisk Pharma       
Insulin regular-isophane  Humulina® 20:80 pen 100U/ml  Lilly  Storage: 4 days (20°C), 48h (25°C), 24h (30°C), 12h (35°C). Once in use: 28 days (25°C)  Bovaira García et al., 20044   
Insulin regular-isophane  Humulina® 30:70 pen 100U/ml  Lilly  Storage: 4 days (20°C), 48h (25°C), 24h (30°C), 12h (35°C). Once in use: 28 days (25°C)  Bovaira García et al., 20044   
Insulin regular-protamine  Mixtard 20 innolet® 100IU/ml  Novo Nordisk Pharma  Storage: 24h at 9–25°C. Once in use: 4 weeks  Cobos Campos et al., 20063   
Insulin regular-protamine  Mixtard 30 innolet® 100IU/ml  Novo Nordisk Pharma  Storage: 24h at 9–25°C. Once in use: 4 weeks  Cobos Campos et al., 20063   
Insulin lispro  Humalog® 100IU/ml vial  Lilly  Storage: 7 days (20°C), 48h (25°C), 24h (30°C), 12h (35°C). Once in use: 28 days (25°C)  Cobos Campos et al., 2006,3 SmPCs (review year not available)   
Insulin lispro  Humalog humaject® 100U/ml pref. pen  Lilly  Storage: 7 days (20°C), 48h (25°C), 24h (30°C), 12h (35°C). Once in use: 28 days (25°C)  Cobos Campos et al., 2006,3 SmPCs (review year not available)   
Insulin lispro  Humalog pen® 100U/ml pref. pen  Lilly  Storage: 7 days (20°C), 48h (25°C), 24h (30°C), 12h (35°C). Once in use: 28 days (25°C)  Cobos Campos et al., 2006,3 SmPCs (review year not available)   
Insulin lispro-protamine  Humalog MIX25 pen® 100IU/ml pref. pen  Lilly  Storage: 7 days (20°C), 48h (25°C), 24h (30°C), 12h (35°C). Once in use: 28 days (25°C)  Cobos Campos et al., 2006,3 SmPCs (review year not available)   
Insulin zinc  Monotard® 100IU/ml vial  Novo Nordisk Pharma  Storage: 24h at 25°C. Once in use: 6 weeks  Cobos Campos et al., 20063   
Interferon 2A  Intron A® 10MIU vial solution  Schering-Plough  7 days  Cobos Campos et al., 2006,3 Bovaira García et al., 2004,4 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Interferon 2A  Intron A® 18MIU pen  Schering-Plough  48h at 25°C  Bovaira García et al., 2004,4 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Interferon 2A  Intron A® 60MIU pen  Schering-Plough  48h at 25°C  Bovaira García et al., 2004,4 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Interferon B-1A  Rebif® 22mcg prefilled syringe  Serono Spain  Storage: 6 days 25°C. Once in use: 1 month  Silgado et al., 2006,2 Cobos Campos et al., 2006,3 Bovaira García et al., 2004,4 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Interferon B-1A  Rebif® 44mcg prefilled syringe  Serono Spain  Storage: 6 days 25°C. Once in use: 1 month  Silgado et al., 2006,2 Cobos Campos et al., 2006,3 Bovaira García et al., 2004,4 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Isoprenaline  Aleudrina® 0.2mg vial  Reig Jofre  6 months at 25°C (at this temperature, reduce expiry 3 months)  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 20044    Specific recommendation 
Lactobacilli  Casenfilus®  Casen Fleet  24Silgado et al., 20062   
Laronidase  Aldurazyme® 500IU vial  Genzyme  6 months at 25°C  Consult lab 26/02/09  916591670 
Latanoprost  Xalatan® eye drops  Pfizer  1 month at 25°C  SmPCs, Bovaira García et al., 20044   
Latanoprost+timolol  Xalocom® eye drops  Pfizer  1 month at 25°C  SmPCs, Bovaira García et al., 20044   
Leuprolide  Eligard®  Astellas Pharma  14 days at room temperature before use  Consult lab 21/12/09  914952700 
Levosimendan  Simdax® 2.5mg/ml  Orion Corporation  Storage time (contact laboratory if exceeded): >25°C: not acceptable15–25°C: 2–3 days8–15°C: 1 week0–2°C: 1 week<0°C: 1 week  Consult lab 21/12/09  915030252 
LHRH  LHRH®  Ferring  15 days at 25°C  Consult lab 16/02/09  917994780 
Organ preservation fluid  Viaspan®  Bristol Myers  Use not recommended 12–24h after breaking chain  Consult lab 18/02/09  914565300 
Lopinavir+ritonavir  Kaletra® oral solution 60ml  Abbott Laboratories  42 days  SmPCs, Silgado et al., 2006,2 Cobos Campos et al., 20063   
Tetryzoline+medroxyprogesterone+chloramphenicol  Colircusi medrivas®  Alcon Cusi  Storage: 15 days 25°C. Once in use: 1 month  Consult lab 20/2/09, Bovaira García et al., 20044  934977000 
Melphalan  Melfalan® 2mg tablets  Lilly  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 21/12/09  916635000 
Methylergometrine  Methergin® 0.2mg/ml  Novartis Farmaceutica  2 weeks  Cobos Campos et al., 2006,3 Silgado et al., 20062   
Methoxy peg epoetin beta  Mircera® 100mcg/0.3ml prefilled syringe  Roche Farma  1 month at ≤30°C. Do not re-refrigerate  Consult lab 21/12/09  913248100  Specific recommendation 
Methoxy peg epoetin beta  Mircera® 150mcg/0.3ml prefilled syringe  Roche Farma  1 month at ≤30°C. Do not re-refrigerate  Consult lab 21/12/09  913248100  Specific recommendation 
Methoxy peg epoetin beta  Mircera® 200mcg/0.3ml prefilled syringe  Roche Farma  1 month at ≤30°C. Do not re-refrigerate  Consult lab 21/12/09  913248100  Specific recommendation 
Methoxy peg epoetin beta  Mircera® 250mcg/0.3ml prefilled syringe  Roche Farma  1 month at ≤30°C. Do not re-refrigerate  Consult lab 21/12/09  913248100  Specific recommendation 
Methoxy peg epoetin beta  Mircera® 50mcg/0.3ml prefilled syringe  Roche Farma  1 month at ≤30°C. Do not re-refrigerate  Consult lab 21/12/09  913248100  Specific recommendation 
Methoxy peg epoetin beta  Mircera® 75mcg/0.3ml prefilled syringe  Roche Farma  1 month at ≤30°C. Do not re-refrigerate  Consult lab 21/12/09  913248100  Specific recommendation 
Muromonab  Orthodone® OKT3  CILAG Gmbh  1 week at 30°C if at least 6 months of expiry period is left. 48h at 25°C if 3 months of expiry period is left  Cuervas-Mons et al., 20046   
Natalizumab  Tysabri® 300mg 1 vial perfusion  Elan Farma  No information available  Consult lab 06/03/09  935677880 
Nonacog alfa  Benefix® 500IU/1000IU  Baxter  1 month at ≤25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Octreotide  Sandostatin® 0.05mg/ml  Novartis Farmaceutica  14 days at <30°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Octreotide  Sandostatin® 0.1mg/ml  Novartis Farmaceutica  14 days at <30°C  Silgado et al., 2006,2 Cuervas-Mons et al., 20046   
Omalizumab  Xolair® 150mg vial  Novartis Farmaceutica  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 18/02/09  933064200 
Oxytocin  Syntocinón® 10IU/ml  Defiante Farmaceutica Lda  3 months at <30°C  Cobos Campos et al., 20063   
Oxytocin  Syntocinon® 10IU/ml  Defiante Farmaceutica Lda  3 months at <30°C  Cobos Campos et al., 20063   
Palivizumab  Synagis® 100  Abbott Laboratories  2 weeks at <25°C  Silgado et al., 2006,2 Sala et al., 20045   
Palivizumab  Synagis® 50  Abbott Laboratories  2 weeks  Sala et al., 20045   
Panitumumab  Vectibix® 100mg vial  Amgen  24h at 25°C  Consult lab 20/2/09  936001900 
Panitumumab  Vectibix® 400mg vial  Amgen  24h at 25°C  Consult lab 16/02/09  936001900 
Pegaptanib sodium  Macugen® 0.3 prefilled syringe  Pfizer  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 04/03/09  932213366 
Pegfilgrastim  Neulasta® 6mg prefilled syringe  Amgen  72h at <30°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Peginterferon alpha 2a  Pegasys® 135mcg prefilled syringe  Roche Farma  7 days  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Peginterferon alpha 2a  Pegasys® 180mcg prefilled syringe  Roche Farma  7 days  Cuervas-Mons et al., 2004,6 Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 20044   
Peginterferon alpha 2b  Pegintron® 100mcg pref. pen  Schering-Plough  18 months at <25°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Peginterferon alpha 2b  Pegintron® 120mcg pref. pen  Schering-Plough  18 months at <25°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Peginterferon alpha 2b  Pegintron® 150mcg pref. pen  Schering-Plough  18 months at <5°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Peginterferon alpha 2b  Pegintron® 50mcg pref. pen  Schering-Plough  18 months at <5°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Peginterferon alpha 2b  Pegintron® 80mcg pref. pen  Schering-Plough  18 months at <25°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Protamine  Protamina® Rovi 50mg vial  Rovi  48h at 25°C – 1 week  Cobos Campos et al., 2006,3 Sala et al., 20045   
Prothrombin  Prothromplex Inmuno® Tim4 600IU  Baxter  6 months  Sala et al., 20045   
Ranibizumab  Lucentis® 10mg vial  Novartis Farmaceutica  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 16/02/09  933064200 
Rasburicase  Fasturtec® 1.5mg vial  Sanofi-Aventis  15 days at 25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 2004,4 Sala et al., 20045   
Risperidone  Risperdal® 25mg  Janssen-Cilag  7 days  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Risperidone  Risperdal® 37.5mg  Janssen-Cilag  7 days  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Risperidone  Risperdal® 50mg  Janssen-Cilag  7 days  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 20045   
Ritonavir  Norvir® 100mg soft capsules  Abbott Laboratories  1 month at <25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 2004,5 Bovaira García et al., 20044   
Rituximab  Mabthera® 100mg vial  Roche Farma  18 days at <30°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Rituximab  Mabthera® 500mg vial  Roche Farma  18 days at <30°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Rocuronium  Esmeron® 100mg vial  Organon Spain  12 weeks at <30°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 2004,5 Bovaira García et al., 20044   
Rotigotine  Neupro® patches  Ucb Pharma  7 days at 25°C  Consult lab 25/08/09  915703444 
Measles-Mumps-Rubella  Vacuna® MSD triple  Sanofi Pasteur MSD  7 days at 25°C  Cobos Campos et al., 20063   
Secretin  Secrelux®  Sanochemia  3 weeks at 25°C  Bovaira García et al., 2004,4 García Vázquez et al., 19977   
Sirolimus  Rapamune® 1mg tablets  Wyeth Farma  24h at 25°C  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Sala et al., 2004,5 Bovaira García et al., 20044   
Somatrophin  Zomacton® 4mg  Ferring  24–48Consult lab 16/02/09  917994780 
Somatrophin  Genotonorm kabipen® 12mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 0.2mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 0.4mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 0.6mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 0.8mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 1mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 1.2mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 1.4mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 1.6mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 1.8mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Genotonorm miniquick® 2mg vial  Pfizer  6 months at 25°C (including use). Do not re-refrigerate  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044    Specific recommendation 
Somatrophin  Humatrope® 12mg cassette  Lilly  6 days at 8–25°C, 72h at 25–30°C, 24h at 30–40°C  Bovaira García et al., 20044   
Somatrophin  Humatrope® 24mg cassette  Lilly  6 days at 8–25°C, 72h at 25–30°C, 24h at 30–40°C  Bovaira García et al., 20044   
Somatrophin  Humatrope® 6mg cassette  Lilly  6 days at 8–25°C, 72h at 25–30°C, 24h at 30–40°C  Bovaira García et al., 20044   
Somatrophin  Norditropin® simplexx 10mg  Novo Nordisk Pharma  24h at <25°C  Consult lab 05/03/09, Bovaira García et al., 20044  913349800 
Somatrophin  Norditropin® simplexx 15mg  Novo Nordisk Pharma  24h at <25°C  Consult lab 05/03/09, Bovaira García et al., 20044  913349800 
Somatrophin  Norditropin® simplexx 5mg  Novo Nordisk Pharma  24h at <25°C  Consult lab 05/03/09, Bovaira García et al., 20044  913349800 
Somatrophin  Nutropin® AQ 10mg (30IU) cassette  Ipsen Farma  Discard (no information available)  Consult lab 21/12/09  936858100 
Somatrophin  Omnitrope® 3.3mg/ml vial  Sandoz Farmaceutica  1 day at 25°C and 15 days at 15°C, 2 weeks at 0°C or between −2°C and −5°C  Consult lab 23/3/09  917401280 
Pulmonary surfactant  Curosurf® 120  Chiesi Spain  24h at <25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 2004,4 Consult lab 17/02/09  934948000 
Pulmonary surfactant  Curosurf® 240  Chiesi Spain  24h at <25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 2004,4 Consult lab 17/02/09  934948000 
Suxamethonium  Anectine® 100mg vial  Glaxo SmithKline  2 weeks at 25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 2004,4 Cuervas-Mons et al., 2004,6 García et al., 20044   
Temsirolimus  Torisel® 25mg vial  Wyeth Farma  24h at 25°C; note batch no., expiry, temperature, exposure time and contact laboratory. (cadena_de_frio@wyeth.com)  Consult lab 20/2/09  913346400 
Tetracosactide  Nuvacthen Depot®  Defiante Farmaceutica  1–3 months at <25°C  García Vázquez et al., 1997,7 Sala et al., 20045   
Tetracosactide  Synacthen®  Novartis Farmaceutica  3–4h at <25°C  Silgado et al., 2006,2 Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Thymoglobulin  Timoglobulina® 25mg vial  Genzyme  24h at <37°C  Silgado et al., 20062   
Thiotepa  Tioplex® 15mg vial  Addiene  3 months at 25°C (Oncothiotepa)  Silgado et al., 20062   
Tipranavir  Aptivus® 250mg soft capsules  Boehringer Ingelheim Spain  Storage: 60 days, 15–30°C. Once in use: 60 days at <25°C  Consult lab 21/12/09  934045100 
Thyrotropin alpha  Thyrogen® 0.9mg vial  Genzyme  1–2 years  Cuervas-Mons et al., 2004,6 Cobos Campos et al., 2006,3 Sala et al., 2004,5 Silgado et al., 2006,2 Bovaira García et al., 20044   
Tobramycin  Tobi® 300mg 56 amp. 5ml  Chiron Iberia  1 month at 25°C  Cuervas-Mons et al., 2004,6 Silgado et al., 2006,2 Bovaira García et al., 2004,4 Sala et al., 20045   
Topotecan  Hycamtin® 0.25mg capsules  Glaxo SmithKline  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 20/02/09  918070301 
Topotecan  Hycamtin® 1mg capsules  Glaxo SmithKline  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 20/02/09  918070301 
Toxin A, Cl. botulinum  Dysport® 500IU vial  Ipsen Pharma  3 days  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Arrixaca, Sala et al., 20045   
Botulinum toxin  Botox® 100Allergan Sau  14 days at 25°C; 7 days at 30°C  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Botulinum toxin  Botulismus-antitoxin Behring®  Esteve  1 week at 37°C  Bovaira García et al., 20044   
Trabectedin  Yondelis® 0.25mg vial  Pharmamar  72h at 25°C  Consult lab 25/10/07  918466000 
Trabectedin  Yondelis® 1mg vial  Pharmamar  72h at 25°C  Consult lab 25/10/07  918466000 
Trastuzumab  Herceptin® 150mg vial  Roche Farma  30 days at 40°C, 3 days at 50°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Arrixaca   
Trientine hydrochloride  Syprine®  Merck Sharp Dohme  7 days  García Vázquez et al., 19977   
Tuberculin  Tuberculina® PPD  Ucb Pharma  6 months at 25°C, 2 weeks at 35°C  Cobos Campos et al., 2006,3 Silgado et al., 20062   
Meningococcal C vaccine  Meningitec® prefilled syringe  Wyeth Farma  24h at <25°C  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 20044   
Diphtheria, tetanus, pertussis vaccine  Boostrix® 0.5ml syringe  Glaxo SmithKline  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 25/08/09  918070467 
DTP and hepatitis B vaccine  Tritanrix®  Glaxo SmithKline  2 weeks at 21°C; 1 week at 37°C. Although, as it is a vaccine, it is recommended to be discarded  Bovaira García et al., 20044   
DtaP vaccine  Infanrix®  Glaxo SmithKline  2 weeks at 21°C; 1 week at 37°C. Although, as it is a vaccine, it is recommended to be discarded  Cobos Campos et al., 2006,3 Silgado et al., 2006,2 Bovaira García et al., 20044   
Haemophilus influenzae b vaccine  Hiberix®  Glaxo SmithKline  2 weeks at 21°C; 1 week at 37°C. Although, as it is a vaccine, it is recommended to be discarded  Silgado et al., 20062, Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Hepatitis B vaccine  Twinrix® adult prefilled syringe  Glaxo SmithKline  Note batch no., expiry, temperature, exposure time and contact laboratory  Consult lab 25/08/09  918070467 
Pneumococcal conjugate vaccine  Prevenar® prefilled syringe  Wyeth Farma  24h at ≤25°C. Although, as it is a vaccine, it is recommended to be discarded  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Rabies vaccine  Rabipur®  Novartis Farmaceutica  1 year at 25°C; 3 months at >37°C; 1 month at >55°C. Although, as it is a vaccine, it is recommended to be discarded  Consult lab 01/04/06  933064200 
Varicella vaccine  Varilrix®  Glaxo SmithKline  1 week at 21°C. Although, as it is a vaccine, it is recommended to be discarded  Bovaria García et al., 2004,4 Silgado et al., 20062   
Hepatitis A vaccine  Havrix® 1440  Glaxo SmithKline  2 weeks at 21°C; 1 week at 37°C. Although, as it is a vaccine, it is recommended to be discarded  Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Hepatitis A vaccine  Havrix® 720  Glaxo SmithKline  2 weeks at 21°C; 1 week at 37°C. Although, as it is a vaccine, it is recommended to be discarded  Silgado et al., 2006,2 Cuervas-Mons et al., 2004,6 Bovaira García et al., 20044   
Meningococcal C vaccine  Menjugate®  Esteve  6 months at 30°C, 1 week at 40°C (without reducing expiry period). Although, as it is a vaccine, it is recommended to be discarded  Cobos Campos et al., 2006,3 Bovaira García et al., 20044   
Hepatitis B vaccine  Engerix-B® 10mcg  Glaxo SmithKline  2 weeks 21°C, 1 week 37°C  Cobos Campos et al., 20063   
Hepatitis B vaccine  Engerix-B® 20mcg  Glaxo SmithKline  3 weeks 21°C, 1 week 37°C  Cobos Campos et al., 20063   
Tetanus and diphtheria vaccine  Diftavax® 40/4IU adult  Sanofi Pasteur Msd  14 days at 25°C  Silgado et al., 20062   
Tetanus and diphtheria vaccine  Ditanrix® 20/2IU adult  Glaxo Smithk  2 weeks at 21°C, 1 week at 37°C  Cobos Campos et al., 20063   
Inactivated polio vaccine  Vacuna Poliomelitica Berna®  Berna Biotech Spain  Temperature ≤25°C: <24h: reduce expiry period by 2 months >24h and <72 h: reduce expiry period by 4 months>72h and <120h: reduce expiry period by 6 months>120h: discard  Cobos Campos et al., 20063   
Vinblastine  Vinblastina® 10mg vial  Stada  21 days at 15°C and 14 days at 25°C  Consult lab 20/2/09  934738889 
Vincristine  Vincristina® 2mg vial  Pfizer  24h at 25°C  Cobos Campos et al., 2006,3 Cuervas-Mons et al., 20046   
Vinorelbine  Navelbine® 20mg capsules  Pierre Fabre Iberica  1 month at <25°C, 15 days at <30°C, can be frozen  Consult lab 20/2/09, Silgado et al., 2006,2 Bovaira García et al., 20044  934833000 
Vinorelbine  Navelbine® 30mg capsules  Pierre Fabre Iberica  1 month at <25°C, 15 days at <30°C, can be frozen  Consult lab 20/2/09, Silgado et al., 2006,2 Bovaira García et al., 20044  934833000 
Vinorelbine  Navelbine® 50mg vial  Pierre Fabre Iberica  1 month at <25°C, 15 days at <30°C, <48h at >30°C or exposed to the light. Can be frozen  Cuervas-Mons et al., 2004,6 Silgado et al., 20062   
Voriconazole  Vfend® 40mg/ml oral suspension  Pfizer  30 days at 25°C (temperature excursions are cumulative, so contact the laboratory for an individual evaluation)  Consult lab 21/12/09  914909900 
Hyaluronic acid viscoelastic  Provisc®  Alcon Cusi  12h at 25°C  Consult lab 26/08/09  934977000 

The number of drugs in each classification was as follows: (A) 65, (B) 47, (C) 30, (D) 47, (E) 12, and (F) 22. There were also specific recommendations for each category, as follows, provided that the time and temperature limits stipulated for each category were not exceeded:

  • A, B, and C: Establish a control and monitoring system by labelling (Fig. 1).

    Figure 1.

    Standard operating procedure for a break in the cold chain.

    (0.7MB).
  • D: Continue in use if it was a one-off break in the cold chain and did not exceed the established maximum time. Otherwise, dispose of or return the drug to the laboratory.

  • E: Dispose of or return the drug to the laboratory.

There were 31 drugs that could not be included in any category, so it is recommended to check the specific information regarding room temperature stability in Table 2.

The information obtained is available on the hospital intranet, in the “manuales de procedimiento” section of the pharmacotherapy portal. There is also a version on the Internet, in the free access pharmacy department portal (see URL at the end of the article).11

Discussion and Conclusions

The methodology used to conduct this review was similar to that used in the aforementioned studies.2–10 However, there are differences in the information given by certain pharmaceutical laboratories. This may be because the drug companies involved have carried out further stability studies during the time between the completions of both reviews.

One problem found was the differences in stability data for the same active ingredient, depending on the laboratory that undertook the study. We agree with Cobos Campos et al.3 who suggested that laboratories should conduct their stability studies under the same temperature conditions to standardise them and facilitate comparison. However, it is important to consult the information available at each centre for the drug product in question.

It was deemed necessary to have stability data for all drugs to be incorporated in the hospital guide upon inclusion, and for the laboratory to provide degradation tables, as a query made when the chain is broken is urgent, and the laboratory cannot guarantee a drug outside its recommended conditions.

When returning drugs to the laboratories, an agreement can be reached with the manufacturing laboratory, especially when the drug cost is high. The manufacturing cost is often significantly less than the most expensive selling price, and in our experience the contribution of the industry in these cases has been very adequate.

One limitation of this review is that the majority of the data found do not specify the possibility of re-refrigerating after breaking the cold chain, or whether these data are valid if there is a second break in the cold chain. For such a case, the manufacturing laboratory should be consulted.

Another limitation is that action has been formalised only for exceeding the maximum proper conservation temperature, but not for freezing.

Lastly, it is important to note that the information contained in this paper is intended as a reference tool for rapid action in those special situations when the cold chain is broken and it is necessary to know whether a drug may be used or not. If in doubt, we recommend contacting the manufacturing laboratory specifying the concrete conditions to which the product has been subjected. Due to the importance of establishing the period of time the drugs have been out of the recommended temperature range and the temperature reached, this information should not be given to other hospital departments, so as to prevent any bad conservation practice. However, it was considered appropriate to have access to it in the “manuales de procedimiento” section of the pharmacotherapy department portal and to inform other pharmacy departments to facilitate action in the case of a break in the cold chain.To summarise, one of the priority functions of a pharmacist is to ensure the correct storage of medicines.12 This requires the availability of updated information on the validity times of thermolabile drugs when the cold chain is broken. It is the responsibility of the pharmacist to establish guidelines for action when incidents occur. This information must be available and updated in the hospital pharmacy department to ensure that appropriate measures are taken.

Conflicts of Interest

The authors affirm they have no conflict of interest.

References
[1]
W.H. Steffen, D.W. Newton, K.W. Miller.
Room temperature and drug stability.
Am J Hosp Pharm, 51 (1994), pp. 406-409
[2]
R. Silgado, M.J. Jiménez, J.M. Ferrari, A. Herreros de Tejada.
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R. Cobos Campos, P. Salvador Collado, A. Gómez Gener, M. Boj Borbones.
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M.J. Bovaira García, L. Lorente Fernández, M.A. de la Rubia Nieto, M.A. San Miguel Zamora.
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Medicamentos termolábiles pauta actuación HUSD 2009 [quoted 2010 Apr 20]. El comprimido. Available from: http://www.elcomprimido.com/FARHSD/MP_MedicamentosTermolabilesPautaActuacionHUSD2009.doc.
[12]
Ley 29/2006, de 26 de julio, de garantías y uso racional de los medicamentos y productos sanitarios. BOE núm. 178, de 27 de julio de 2006.

Please cite this article as: Periáñez Parraga L, et al. Medicamentos termolábiles. Protocolo de actuación en la rotura de la cadena de frío. Farm Hosp. 2011;35(4):190.e1–190.e28.

Copyright © 2010. SEFH
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