Subcutaneous Route for Drugs and Fluids - PowerPoint Presentation

Slide1

Subcutaneous Route for Drugs and Fluids

Annette O. Arthur PharmD

Department of Emergency Medicine

University of Oklahoma School of Community Medicine

Slide2

Disclosures

Co-investigator on a study funded by

Halozyme

Therapeutics, the manufacturer of the FDA approved human recombinant

hyaluronidase

(

Hylenex

™). The manufacturer had no control over the study design or reporting content.

Slide3

Objectives

Compare the pharmacokinetics of IV, IM and SC administration of fluids and medications

Discuss the emerging methods of SC infusion

Discuss proper SC technique

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Contents

Introduction

Pharmacokinetics

Therapies

Historical uses

Emerging uses

SC access technique

Advantages/Limitations

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Intravenous (IV)

Intramuscular (IM)

Intraosseous

(IO)

Subcutaneous (SC)

Introduction:

Parenteral Routes

Slide6

Introduction: Hypodermoclysis

Old term

for Subcutaneous (SC) fluid infusion

Common in early to mid 1900’s

Interstitial

matrix a barrier to

diffusion

Adverse events with hypertonic solutionsDevelopment of modern IV catheter

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Introduction:

Skin Structure

Slide8

Introduction: Extracellular matrix

Located in the hypodermis

Maintains architecture and controls fluid flow

Collagen fibrils and elastin – structure

Viscoelastic gel – fluid flow

-

Glycosaminoglycans

Hyaluronic AcidLimits SC injection to no more than 2mls

Tissue distortionIncreases injection pressure

Slide9

Introduction: Hyaluronidase

Found in

nature

to increase the dispersion of substances (sperm, toxins, venoms, bacteria)

Initially derived from

bovine

testes

Use traced back to 1928Many impurities leading to increased capillary permeability and allergic reactions Human recombinant hyaluronidase –

HRHFDA approved 2005

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Introduction: Hyaluronidase

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Introduction: Hyaluronidase

HRH Facilitated

D

rug

T

herapy

Dexamethasone

FamotidineGlycopyrrolateHaloperidol

HydromorphoneLidocaineMagnesium

MidazolamOndansetronPotassiumSufentanil

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Pharmacokinetics: Terms

C

max

- maximum concentration

T

max

– time to maximum concentrationt1/2 – elimination half-lifeAUC – Area under the serum concentration-time curve

Bioavailability (F) – the proportion of drug absorbed into the circulation and available for physiologic action

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Pharmacokinetics: IM vs SC

S

imilarity in the absorption and efficacy between IM and SC administration

C

max

▪

AUCTmax ▪ t1/2

IM may have variable absorption depending on blood flow and muscle massIM absorption is unpredictable in infantsInsufficient muscle toneInsufficient vascularity

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C

max

– Higher IV

than

SC

T

max – Faster IV than SCAUC – IV and SC similart1/2 – IV and SC similar

Bioavailability – SC injected meds are generally

Pharmacokinetics: IV vs SC

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Pharmacokinetics

Time (

hrs

)

Concentration (mcg/ml)

IV

SC

Slide16

Pharmacokinetics: SC with HRH

C

max

–

Increased

T

max

– FasterAUC – IncreasedBioavailability – Increased

Moves SC PKs closer to IV

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Pharmacokinetics:

SC with HRH

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Therapies: Historical uses

Pediatric rehydration

Palliative care

(fluids and pain meds)

Deferoxamine

Iron chelating agent

Haemochromatosis

Pts

/caregivers start SC access and administer med w/ ambulatory pump over 8-10 hours 5-7 days/wk

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Therapies: Emerging –

mAbs

Trastuzumab

– 1998 FDA approved

HER2+ breast cancer, early and metastatic

HannaH

study, 2012, Ismael et alWynne et al study, 2013

PrefHer, 2013, Pivot et alRituximab

– 2006 FDA approvedTargets CD20; indicated for non-Hodgkin’s lymphoma and chronic lymphocytic leukemiaSABRINA study, 2013,

Davies et al

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Therapies: Emerging – ABX

Ceftriaxone

Third-generation cephalosporin

Broad spectrum; gram (-) and gram (+) activity

Once daily dosing

Typically administered IV or IM

IV more costly, inconvenient (hospital or Dr. visit)

IM costly, inconvenient, and painful

Study published in 2010, Harb et alSafety and PKs of IV & SC

SC w/ HRH and without

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Therapies: Emerging – ABX , cont.

Ertapenem

Long-acting, parenteral

carbapenem

Mainly indicated for community/hospital-acquired infections (not

Pseudomonas or

Acinetobactor

)Daily dosing, IM or IV administrationStudy in France by Frasca, 2010

Compare PKs after 30 min IV & SC infusionsSC did not include HRH

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Therapies:

Emerging –

IgG

1952 –

IgG

replacement

Tx

first given1950’s – 1970’s – IgG given by IM injection1980’s – IV became the most common route

2006 – SC formulation FDA approved2010 – higher concentration SC FDA approved2013 – IgG + HRH in clinical trials

SC → IM → IV → SC

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Therapies: Emerging –

IgG

cont.

IGIV – monthly infusions

IGSC – weekly home infusions, multiple sites

IGHy

– monthly infusions, single site, at homeWasserman study, 2012IGHy bioequivalent to IGIV

Main AE with IGHy – localSystemic AE IGIV (25%) > IGHy (8.3%)

HA, fatigue, n/v, fever, chills

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Therapies:

Emerging – Pain

Mngt

Morphine Sulfate

Moderate to severe pain

Pt controlled analgesia (PCA)

SC vs IV

INFUSE Morphine study,

Thomas

et al

SC Morphine +

Ketoprofen

Moselli

et al,

2010

Continuous SC MS w/w/o

Ketoprofen

for cancer pain

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Therapies: E

merging – Anti-Emetic

Ondansetron

Selective serotonin-blocking

agent

IM, IV, PO formulas

Approved for n/v

Study of SC use in Pregnancy (

Klauser

, 2011)

AE’s – mild and transient

PKs similar to other discussed drugs

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Therapies: Emerging –

Hydration

Pediatric

ORT is first line treatment for dehydration

15% - 20% unable to perform ORT

SC + HRH infusion of fluids safe & effective

SC + HRH more cost-effective than IV

Adult

Most studies were conducted in the 1980’s-1990’sStudies in 2005 and 2 in 2007SC+HRH is safe, well-tolerated, and cost effective

Slide27

Therapies: Emerging – Insulin

Hompesch

, 2011

Type 1 diabetes mellitus patients

Prandial

insulins

-

Lispro & Regular human insulinPeak exposure inc’d 35% and 66% with HRHTime to peak

dec’d significantlyMorrow, 2013Healthy volunteers

HRH + lispro/aspart/glulisine insulins

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Therapies: Mass Casualty Events

Ease of SC access

Minimal training required; no special equipment

Adverse conditions in the field

Poor lighting, cramped spaces, moving vehicles

#

Pts

> # medical providersMCI injuries often require quick fluids/meds

A variety of injuries and illnessesCrush injuries

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Case report: Severe Hemorrhage

57-yr old lady, with secondary progressive

MS

ED

– weakness, clammy, fever

Dx

– right basal pneumoniaTx – IV Abx, fluids, prophylactic LMWH

Swallow assessment – signs of silent aspirationOral feedings – unable to maintain hydration

SC fluid infusion – replace fluidsDay 30 – started bleeding at sitePt died 7 hours later

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Choose

site

,

prep

skin,

pinch

Insert

IV cath (22-24 g); 45° angleSecure catheter with tape/transparent drsgif using – Inject HRH, 150 units/1 ml Attach Standard IV tubing & secure

Begin to infuse fluids a/o medsRate gravity drivenDon’t

be surprised by some soft swelling at the site of the infusion; this is normal

Technique: Overview

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Technique:

Locations

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Technique: Skin pinch

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Technique:

Skin pinch

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Technique: Skin pinch, cont.

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Technique: Catheter placement

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Technique:

Catheter placement

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Technique: Secure catheter

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Advantages: SC vs IV/IM

Smaller needle/IV catheter

Less pain

More sites for injection/infusion

Less frequent site change

Avoids infusion reactions

Systemic infection, less concern

Administration at homeLess cost

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Limitations: SC vs IV/IM

Limited volume (1-2mls)

Drug trapping

Irritants

Retention

Home administration

Slide40

Current studies

Psoriasis

Asthma

Osteoporosis

Crohn’s

Dz

RABreast CancerHodgkin’s lymphomaCLL

Multiple sclerosisAlzheimer’s DzPain management

Diabetic kidney DzBone healingSLE

TTPEtc.

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Conclusion

Hypodermoclysis

has been used for many decades

Pharmacokinetics

are well understood

Bioavailability

similar to IV administration

HRH co-administration improves PKUses: fluid resuscitation, mAbs, ABXs,

IgG replacement, insulin, pain management, anti-emetics, and MCISimple techniqueAdvantages/disadvantages

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Questions

?