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INCOMPATIBILITY

OF IV DRUGS :

SOME CLINICAL

HIGHLIGHTS

Dre Caroline Fonzo-Christe

Pharmacie des HUG

2

FACULTY DISCLOSURE

No, nothing to disclose

x Yes, please specify:

Company NameHonoraria/

Expenses

Consulting/

Advisory

Board

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Research

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Patent

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/ Equity

Position

EmployeeOther

(please specify)

Doran InternationalInvited

speaker

Pall companyInvited

speaker

3

WHAT ARE WE TALKING ABOUT?

Addition of midazolam

4

WHAT ARE WE TALKING ABOUT?

Addition of midazolam

WHAT ARE WE TALKING ABOUT?

B.Braun, KIK 2.1 2002 and Drug incompatibility 2011 www.safeinfusiontherapy.com

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HUG

caspofungine + heparine

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SOME QUESTIONS

• A theoretical problem?

• An old stuff?

• What are the clinical consequences?

• A pharmacist issue?

• What can we do? Can YOU do something

for this issue?

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CONTEXT

Environment

• Temperature

• Light

Material

• PVC (DEHP)

• Silicone

•…

Drug A

Solvent +

excipients

Drug B

Factors

• Concentration

• Contact time

Solvent +

excipients

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TYPE OF REACTIONS

Physico- chemical

• Acid-base reactions (pH)

• Solubility

• Emulsion cracking

• Oxydo-reduction

• …

Consequences

• Precipitates (visible)

• Colour change (visible)

• Gaz production (visible)

• pH change (invisible)

• concentration (invisible)

• Catheter occlusion

• Renal and pulmonary embolism

• therapeutic effect

• Toxic effects (peroxides) patient

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ACIDS AND BASES

From: KIK 2.1,

BBraun, 2002

Acid drug molecule basic drug solution

Basic drug molecule acidic drug solution

Don’t mix or infuse

on Y-site

acidic with basic

drug solutions!

Molecule Drug

solution

Molecule Drug

solution

Furosemide (acid) pH 9 Furosemide (acid) pH 9

Vancomycin (base) pH 3 Midazolam (base) pH 4

From: KIK 2.1, BBraun, 2002

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SOLVENT (DILUENT)

Furosemide in Glucose 5% From: KIK 2.1, BBraun, 2002

Glucose 5%-20% pH = 3.5 - 6.5 amiodarone, amphotericine B

NaCl 0.9% pH = 5.0 - 7.0 aciclovir, phenytoin

Solvent pH Appropriate for

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LIPID EMULSION

reversible

irreversible

Coalescence :

pH

conc. AA

Electrolytes with

high valence (Ca2+,

Mg2+, PO43-)

Lipid emulsion is

not water!

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SOLUBILITY

“Pastis effect”

drug excipient

amiodarone Cordarone® polysorbate (tween)

paracetamol Perfalgan® mannitol, phosphate, NaOH

esomeprazole Nexium® NaOH, EDTA

phenytoin Phenhydan® glycofurol-75, EDTA

clonazepam Rivotril® propylene glycol, acetic acid

Co-solvent and/or adjusting pH

can increase the solubility of

drugs in solution

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CLINICAL INCIDENTS

Knowles JB et al. JPEN 1989;13:209-13

Hill SE et al. JPEN 1996;20:81-87 McNearney T et al. Dig Dis Sci 2003;48:1352-4

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CALCIUM COMPLEXATION

Insoluble

Ceftriaxone – Calcium

Complex

Bradley JS et al. Pediatrics 2009;123:609-13

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RECENT DATA: DRUG - DRUG

Kalikstad B et al. Arch Dis Child 2010;95:745-748

Zhao B et al. Am J Health-Syst Pharm 2014;71:901-902

Lack of DATA

in NICU

Case-reports of

catheter

occlusion

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RECENT DATA: DRUG - SOLVENT

Christensen RD et al. Arch Dis Child Fetal Neonatal 2012;97:F3

Stark MJ et al. Arch Dis Child Fetal Neonatal 2012;97:F62-64

Blood always

alone

SOME QUESTIONS

• A theoretical problem?

• An old stuff?

• What are the clinical

consequences?

• Not only, also a real one

• Yes, well known problem

since the eighties, but still

a current problem in the

practice

• May lead to precipitates

and renal and pulmonaryembolism

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AIR POLLUTION

Visible range:

> 50 m

Erythrocytes:

about 7.5 m

Capillary:

8-10 m

Brook RD. Clinical Science 2008;115:175–187

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CLINICAL CONSEQUENCES

Mechanical local

endothelial

damage

Thrombotic and

inflammatory

response

Brook RD. Clinical Science 2008;115:175–187

S.I.R.S

Predisposition

to SIRS?

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IN-LINE FILTRATION AND SIRS

Jack T et al. Intensive Care Med 2012;38:1008–1016

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COSTS

Jack T. et al Intensive Care Med 2012;38:1008–1016

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IN PRACTICE

Austr Prescr 2008;31:98-101

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IN VITRO TESTING

Bouchoud L et al. JPEN J Parenter Enteral Nutr. 2013;37:416-24

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TPN: CALCIUM/PHOSPHATE

Bouchoud L et al. JPEN J Parenter Enteral Nutr. 2010;4:542-5

• Phocytan ® (Glucose-1-phosphate Na)

• Glycophos ® (Glycerophosphate Na)

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TOOLS

http://pharmacie.hug-ge.ch/infomedic/utilismedic/HUG_CompatAdm_DCI.pdf

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I-TOOLS, DATA-BASES

http://fr.appbrain.com/app/injectable-medicines/air.coim, http://www.ahfsdruginformation.com,

http://www.theriaque.org, http://www.kik-service.de, http://www.stabilis.org, https://www.kingguide.com

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HUG: IN-LINE FILTERS

http://pharmacie.hug-ge.ch/infomedic/utilismedic/filtres_USI.pdf

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CHRU LILLE (FRANCE)

Foinard A et al. Anesth Analg 2013;116:101-6

Perez M. CHRU Lille

SOME QUESTIONS

• A pharmacist issue?

• What can we do? Can

YOU do something for this

issue?

• Yes, it is– In vitro testing

– Drug incompatibility charts

– Bedside teaching

But also…• Multidisciplinary team

working– Infusion material: In-line

filters, new devices

– Clinical pharmacist

physician

pharmacist

nurse

biomedical,

technicians…

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ARE YOU READY TO INVEST?

Thank you

for your

attention