Glasgow Royal Infirmary Pharmacy Department

PHARMACEUTICAL ASPECTS OF INTRAVENOUS DRUG ADMINISTRATION Glasgow Royal Infirmary Pharmacy Department

Differences IV  ORAL route IV administration leads to: • Higher peak concentrations • Greater total quantity of drug absorbed • Avoids 1st pass metabolism • However requires more training, knowledge, skills and precautions Conc. time

IV route - Advantages • Emergency situations / immediate response e.g. adrenaline in cardiac arrest. • Loading dose e.g.digoxin, phenytoin • Patient unable to swallow or tolerate other routes • Sustained drug levels required • Drug cannot be given by another route because of its chemical property e.g. cytotoxics, cefotaxime

Less painful than I.M. injection. • Administration can be stopped quickly • Allows dosing of unconscious, uncooperative and uncontrollable patients. • To achieve effects unattainable by oral administration.

IV route - Disadvantages •  Risk of toxicity • Risk of embolism • Risk of extravasation/phlebitis • Fluid overload • Problems with compatibility + stability • Risk of microbial contamination • Increased cost • More training required

BOLUS 3-10 minutes • Quick/easy/economical • Tendency to administer too quickly causing damage to veins. • Sudden anaphylactic reactions • Only limited volumes can be administered

Intermittent IV INFUSION 20-120 minutes • One-off or repeated doses • E.g. Gentamicin, vancomycin, erythromycin • High plasma concentration achieved rapidly over longer periods.

Continuous IV INFUSION • Delivers constant level of drug • Used for drugs with a rapid elimination rate or a very short half-life e.g. midazolam BUT • Fluid overload, incompatibility, contamination, incomplete mixing, phlebitis and rate calculations can be problematic.

Formulation of I.V. drugs • Reconstitution required -Dry powder e.g. amoxicillin -Allows prolonged storage BUT - Is time consuming - Risk of contamination, foaming, glass particles, pressurised vials.

Solutions needing further dilution • e.g. Ranitidine, Amiodarone • No reconstitution necessary BUT • Time consuming • Prone to vacuum/pressure problems • Can cause glass breakage • Risk of microbial contamination.

‘Ready to use’ • No further dilution needed • Come in bags/small volume amps/syringes e.g. metoclopramide, adenosine, morphine PCAs • Easy to use & time saving • Minimal microbial contamination BUT • Microbial contamination • Fluid overload

Factors influencing Stability & compatibility A proportion of the drug will be lost between time of preparation and entry into the bloodstream by degradation, precipitation or an interaction.

Degradation • By hydrolysis in aqueous solution • May be accelerated by pH change • Minimised by using reccomended diluent

Photodegradation • Breakdown by light. e.g. Vitamin A, sodium nitroprusside, liposomal amphotericin. • May not be clinically important provided direct exposure to strong daylight is avoided e.g. furosemide.

Precipitation • Precipitates are inactive but harmful: can block catheters, damage capillaries and cause emboli. • May be transparent or pale • Affected by differences in pH • Anions and cations mix to form ion pairs • Most drugs are more soluble as temp. increases

Blinding of drugs to plastics • Most equipment made from plastic • Drug binding difficult to predict as it depends on: Conc. Flow rate, vehicle, surface area, temp. pH and time. • Care with insulin, diazepam, nitrates....

Leaching of plasticisers • Oils and surfactants contained in PVC bags can leak out and affect compatibility and stability of drugs. e.g. Ciclosporin infusion must be used within 6 hours as polyethoxylated castor oil in the solution causes phthalate to leach from PVC.

Add one drug at a time following manufacturers advice Mix thoroughly to avoid layering Examine solution regularly Add most concentrated or most soluble additive first Strongly coloured solutions will hide reactions Observe patient for ADR’s Summary

Intravenous Antibiotics State for each of the following: Diluent & volume required for reconstitution Volume required for dose Type of injection Gentamicin 260mg Erythromycin 750mg Co-amoxiclav 1.2g Metronidazole 500mg Tazocin 4.5g

Example (1) • How would you prepare and administer Flucloxacillin 1g IV? Each 1g vial should be reconstituted with 20ml WFI (SPC) Add 20ml reconstituted solution to 100ml NaCl 0.9% or glucose 5% (BNF) Can be given as an infusion over 30-60min. or bolus injection over 3-4 min. (BNF & SPC)

Example (2) • How would you prepare & administer Vancomycin 1250mg • Each 500mg vial should be reconstituted with 10ml WFI – Use 3 vials (BNF Appendix 6) Got 1500mg  30ml 1250mg  1250 x 30 / 1500 = 25ml Conc. of infusion fluid must be ≤ 5mg/ml (BNF) Therefore put 25ml into 250ml of Nacl 0.9% or Glucose 5% Must be given as an infusion (SPC & BNF)

References to use • BNF appendix 6 • BNF monographs • SPC (www.emc.medicines.org.uk) • Technical leaflet • JHO handbook • Medusa I.V. drugs guidance manual (www.medusa.wales.nhs.uk) • Ward clinical pharmacist • Medicines information (ext 24407)

How would you prepare and administer: Gentamicin 260mg Co-amoxiclav 1.2g Tazocin 4.5g Erythromycin 750mg Metronidazole 500mg

Answers • Gentamicin 260mg 4 x 80mg/2ml vials. Withdraw 6.5ml and add to 100ml NaCl 0.9% or Glucose 5%. Give over 30-60 min. • Co-amoxiclav 1.2g 1.2g vial reconstituted with 20ml WFI. Bolus (3-4min.) or infusion in 50-100ml NaCl0.9% given over 30-40min.

Answers (cont) • Tazocin 4.5g vial reconstituted with 20ml WFI or NaCl 0.9%. Bolus (3-5min.) or infusion in 100ml NaCl 0.9% over 20-30min. • Erythromycin 750mg 1000mg vial reconstituted with 20ml WFI. Withdraw 15ml (750mg) and add to 250ml NaCl 0.9%. (Cannot get 150ml bag!!) Infuse over 60min.

Answers (cont.) • Metronidazole 500mg 100ml bag 5mg/ml = 500mg. Infuse over 20 min.

Glasgow Royal Infirmary Pharmacy Department