ASEPTIC DISPENSING TECHNIQUES/DRUG- NUTRIENT INTERACTIONS

Transcription

1 ASEPTIC DISPENSING TECHNIQUES/DRUG- NUTRIENT INTERACTIONS HARBANS KAUR DHILLON PRESIDENT OF PENSMA KUALA LUMPUR MALAYSIA PENSA 2007

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4 University Malaya Medical Centre Kuala Lumpur

5 ASEPTIC DISPENSING Ppn & supply of sterile medical products that require some dilution or other manipulation before administration Prepared in Pharmacy by trained technicians, assistants & pharmacists Environmentally controlled conditions

6 WHY DO IT? Reduces risk of microbial & particulate contamination Ensures correct dilution Ensures stability & compatibility Ensures appropriate route & rate of administration Saves clinical staff time on the wards Cost savings

7 ADVERSE EVENTS & PATIENT SAFETY Concerns on adverse events & patient safety Regulatory bodies & professional associations actively developing & revising standards of practice Compounding of sterile preparations such as PN is an integral part of any health-system setting There are inherent dangers in compounding sterile products Adverse events have resulted because of: Incorrect ingredients Inaccuracies Contamination Poor aseptic technique

8 ENVIRONMENT Sterile compounding procedures vary Lack of uniformity & changing technology Over the past 25 years pharmacists have been publicly cited for harming patients because of compounding errors New technology & procedures in the use of such technology challenge the pharmacist s s ability to compound, package & label products appropriately

9 ASHP SURVEY 96% of hospital pharmacies did sterile extemporaneously compounded products 61% did batching 99.4% compounded using a LAFH 75% kept the LAFH in limited access areas 50% certified the LAFH every 6 months 33% sampled environmental microbial bio- burden

10 ASHP SURVEY 33% of pharmacists used final filtration to sterilize preparations 50% never tested for chemical purity, potency, sterility or pyrogenicity Less than 33% tested their pharmacists/technicians on aseptic technique Majority of pharmacists could not determine whether they were compounding safe & effective sterile products

11 POTENTIAL MICROBIAL HAZARDS Glass ampoules broken with a paper towel Preparation undertaken on a non-sterile cardboard tray Antibiotic syringe placed uncapped on a cardboard tray after preparation & carried through the ward to the patient A Risk Assessment of the Preparation of Parenteral Medicines in Clinical Areas by MJ Munro BW Millar Perth Royal Infirmary, Perth Hospital Pharmacist July/August 2003

12 POTENTIAL MICROBIAL HAZARDS No handwashing Incorrect swabbing technique Vial punctured immediately after swabbing Air drawn from the room into a syringe Lack of no touch technique Sink used to dispose of excess drug in the syringe during preparation A Risk Assessment of the Preparation of Parenteral Medicines in Clinical Areas by MJ Munro BW Millar Perth Royal Infirmary, Perth Hospital Pharmacist July/August 2003

13 POTENTIAL FOR MEDICATION ERRORS IN PREPARATION Staff interrupted during preparation No check of the medication chart by a colleague Drug or diluents not checked Calculations not checked Dose measured inaccurately No check that the drug was dissolved before drawing back into a syringe Syringe not labeled Syringe labeled, but no patient name A Risk Assessment of the preparation of Parenteral Medicines in Clinical Areas by MJ Munro BW Millar Perth Royal Infirmary, Perth Hospital Pharmacist July/August 2003

14 QUALITY ASSURANCE The essence of quality assurance is proving that you are really doing what you say you are doing L.Trissel Risk assessment or gap analysis of compliance Develop an action plan for each area

15 BEYOND THE PHARMACY Monitoring product quality after it leaves the pharmacy Training for patient & patient giver Ensure proper administration techniques Handling of storage condition issues & arrangements for disposal/returns Monitoring of adverse events

16 PART 2 DRUG-NUTRIENT INTERACTIONS

17 STABILITY CRITERIA OF TPN SOLUTIONS No changes to the size of lipid & their size distribution No precipitation Bioavailability of all components Absence of chemical reactions between components

18 COMPONENTS OF A TPN BAG Amino Acid Solution Glucose 1 Lipid Emulsion 4 Electrolytes 8 Na, K, Mg, Ca, P, Cl, Sulphate, acetate, gluconate Trace Elements 4-7 Zn, Cu, Mn,, Cr, I, Se, Mo, F. F Vitamins 12 Water Soluble, Lipid Soluble Total 44 52

19 UNWANTED MATERIALS IN TPN BAGS Chemical precipitation From instability of TPN admixtures From incompatible drugs/electrolytes coming together in the set Emulsion Instability Lipid emulsions for TPN Emulsified drug formulations Foreign Material Shedding from container Glass U.F.O.

20 Intralipid Chylomicrons 0.2 % 1-2 micron 99.8 % < 1 micron

21 FACTORS AFFECTING STABILITY OF THE LIPID EMULSION IN AIO Amino acids Buffering capacity Protective effect No substitution without validation Glucose solutions High concentration is destabilizing Electrolytes Careful with Ca & Mg!

22 COALESCENCE ZETA POTENTIAL LOW ph HIGH GLUCOSE

23 PRECIPITATION Solid matter formed in solution Calcium + phosphate precipitates when concentrations of CaPO 4 > solubility limits Phosphate + trace elements Trace elements + amino acids

24 INCOMPATIBILITIES WITH BAG MATERIAL TPN bags must be made without softeners Lipids may extract phthalates from PVC bags EVA & poly-olefines olefines do not contain softeners

25 CALCIUM & PHOSPHATE PRECIPITATES Immediate precipitation Time mediated precipitation Courtesy of Monique delange

26 PHARMACEUTICAL CONSIDERATIONS & PARENTERAL NUTRITION Drug/nutrient interactions e.g. chemical/physical compatibility? Drug or its formulation interactions with lipid emulsion (including partitioning of drug) Drug stability in the TPN solution i.e. degradation due to ph, oxidation etc. Adsorption or absorption of drug to container

27 PHARMACEUTICAL CONSIDERATIONS & PARENTERAL NUTRITION Drug remains available? Stability of the TPN solution adversely affected? Toxic/adverse effects due to drug addition? Bioavailability/appropriate pharmacokinetics of drug administration? Product liability? Cost of studies expensive due to scope & complexity

28 IRON DEXTRAN & TPN Cracking of fat 21 hours after compounding formation of a fat layer and a 1.2 µm m filter blocking with iron dextran 100mg in 2 L of TPN - Vaughan et al No evidence of physical incompatibility with PN up to 48 hours storage at room temperature with iron dextran 4mg in 2 L of TPN - Yu-Hsing et al

29 HEPARIN Reduces the incidence of septic complications Prevents central line thrombosis by hindering the formation of a fibrin sheath around the feeding catheter Heparin destabilises fat emulsions formation of heparin/calcium/lipid complexes Bovine or Porcine origin Composition varies from batch to batch, stability only on batch tested Effect on stability UNPREDICTABLE Rattenbury (1989) & Barnett et al (1996)

30 INSULIN (SOLUBLE) Not reported to be rapidly degraded in AIO admixtures No effect on fat emulsion stability Adsorption to container surface can be significant Adsorption rapid after addition ~ minutes No flexibility ~ flow-rate

31 CIMETIDINE Stability of cimetidine (Tagamet ) investigated in TPN solutions containing different AA sources (Freamine111, Vamin 14 & Aminoplex 12) Stored at 5 C 5 C in EVA bags for 28 days Stability was measured by HPLC Results showed that cimetidine was compatible & chemically stable (<5% degradation) for at least 28 days Long Long term stability of cimetidine in TPN M.C. Allwood & H.J. Martin 1996 Journal of Clinical Pharmacy and Therapeutics Volume 21 Issue 1

32 ADDITION OF DRUGS TO TPN Further in-depth depth studies required Consider clinical effectiveness & pharmaceutical stability criteria DO NOT extrapolate results from literature to all regimens Co-infusion infusion via a Y-port Y can overcome many problems, but requires a filter & care

33 SOME USEFUL TIPS TPN does not need to run 24 hours a day Can be interrupted Use saline to flush lines, run in drugs & flush again with saline Y-connectors can be used, with caution Contact pharmacist when in doubt

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