iv drug incompatibilities
TRANSCRIPT
Jonathan B. Hjelm, PharmD, BCPS, BCNSP, CGP
Clinical Pharmacist
Pharmastar PBM
Objectives1. Define IV compatibility and incompatibility.
2. Where can incompatibilities occur?
3. What can be done to prevent them?
4. How do you know if a combination of drugs are compatible?
I. What questions to ask
II. Where to look for compatibility data
III. How to interpret compatibility data
Background Drug stability and compatibility are critically
important in the provision of safe and effective drug therapy
Multiple drugs may be administered simultaneously to a critically ill patient and determining the compatibility of those agents is of great importance.
It is estimated that over 30% of the commonly utilized drugs are incompatible or unstable when added or combined with usual fluids or agents.
Definition Incompatibility = is a reaction between drugs that after
mixing are no longer safe or effective for the patient.
Characteristics of incompatibilities: Color Change
Hazy Appearance
Precipitations
NOT all incompatibilities are dangerous, some are just normal.
Color Change
Imipenem-cilastatin or dobutamine may show some color change but NOT a sign of incompatibility.
Hazy Appearance
When ceftazidime is reconstituted, carbon dioxide gas is released and can cause a hazy appearance.
Precipitation
The precipitate that forms when paclitaxel is refrigerated dissolves again at room temperature.
Contributing Factors Light
Amphotericin B, cisplatin, and metronidazole must be protected from light.
Temperature Cefazolin is stable at room temperature for 24 hours but
under refrigeration for 14 days
Dilution Up to 10 mEq of Calcium can be added to each liter of TPN
containing 20 mEq of PO4.
Concentration dependant Bactrim 5 ml/75 ml D5W stable for 2 hours, whereas 5 ml/125
ml D5W is stable for 6 hours
Buffer capacity, pH, and Time Amino acid composition and concentration in TPN
Types of Incompatibilities
1. Therapeutic Incompatibility
2. Physical Incompatibility
3. Chemical Incompatibility
4. Drug IV Container Incompatibilities
Therapeutic Incompatibility The result of pharmacological effects of several drugs
in one patient (a.k.a. drug interactions).
Mechanisms
1. Pharmacokinetic: absorption, distribution, metabolism, excretion (e.g. Ciprofloxacin and Maalox).
2. Pharmacodynamic: antagonism/ synergism (e.g. Coumadin and Vitamin K)
Example Intervention
Heparin and antibiotics Best to avoid mixing heparin with IV antibiotics since heparin can affect the stability of certain antibiotics (e.g. aminoglycosides)
Physical Incompatibility The incompatibility that is more on solubility changes
and container interactions
Type Ways to Prevent
Insolubility -Do not administer a precipitate forming drug-Avoid mixing drugs prepared in special diluents with other drugs- In administration of multiple IV medications, prepare each drug in a separate syringe
Sorption Phenomena
Gas Formation
Solution pH
Physical Incompatibility Physical precipitation of Midazolam as a result of
unfavorable pH.
Chemical Incompatibility Results from the molecular changes or rearrangement
and leads to chemical decomposition
Type Ways to Prevent
Hydrolysis Store drugs in moisture proof containers or use desiccants
Oxidation Reaction Store drugs in amber bottles
Reduction Reaction Keep away from reducingagents
Photolysis Use light proof containers
Chemical Incompatibility Chemical precipitation of Midazolam and Ketamine
Drug-IV Container Incompatibility Incompatibility that arise from the chemical reaction
of the drug and the intravenous container
Type Definition
Adsorption The property of a solid/liquid to attract and hold to its surface a gas, liquid, solute, or suspension (e.g. Propofol)
Factors Causing IV Incompatibility
Type Intervention
Difference in pH Refer to drug compatibility tables
High Concentration Determine the chemically compatible concentration of both drugs
Temperature Refrigerate the IV admixture if not used within 1 hour after mixing or leave at room temperature to avoid clouding and cracking
Order of Mixing Separate addition of ingredients or drugs (e.g. always add phosphorous after calcium to TPN)
Length of Time in Solution Refer to extended stability charts
Health Consequences Consequences for the patient:
Damage from toxic products
Particulate emboli from crystallization and separation
Tissue irritation due to major pH changes
Therapeutic failure
Little published information about frequency of drug incompatibility reactions
One PICU study showed 3.4% of drug combinations were incompatible and potentially dangerous
Clinical incompatibilities can contribute up to 25% of medication errors
Up to 80% of IV drug doses were prepared with the wrong diluent
Financial Consequences Adverse effects of drug incompatibilities extend
patients’ hospitalization and the total costs for hospitals.
Severe respiratory complications caused by toxic drug-drug interactions may lead to an additional healthcare costs of up to $76,500.
Preventive Strategies Always check for compatibility
Standardize protocol for drug preparation
Check for alternative modes of administration
Separation of drug doses by time and place
Usage of multi-lumen catheters
Use in-line filters
Checking IV Compatibility
IV Compatibility Chart
Parenteral Nutrition (PN) Three factors for incompatibilities
with parenteral nutrition
1. Precipitation of calcium and phosphate
2. Creaming/Cracking of the lipid emulsion
3. Addition/simultaneous application of drugs to/with the PN.
Incompatibility Between Drugs and PN
Four criteria for drugs commonly added to PN admixtures (e.g. insulin, heparin, and Pepcid)
1. Stable dosage regimen over 24 hours
2. Pharmacokinetic profile supporting 24-hour infusion
3. Stable PN solution infusion rate
4. Documented chemical and physical stability over 24 hours
Cracked TPN
Separation of the oil and water components of the emulsion
Coalescence Fusion of small triglyceride particles into larger
particles
Avoiding Incompatibility with PN Never use PN for electrolyte therapy
Be familiar with manufacturers’ recommendations
Add divalent cations (calcium and magnesium) and phosphate as organic bound salts (e.g. gluconate).
Do not add drugs or Iron to PN
May piggy back lipids separately from 2-in-1 PN
Avoid Y-site administration of drugs with PN
Calcium phosphate solubility curve for TPNs
Automated TPN Compounding
Where To Look For Compatibility Data
Must use professional judgment when evaluating different reference sources.
Ways to Prevent or Minimize Incompatibilities
1. Mix thoroughly when a drug is added to the preparation.
2. Minimize the number of drugs mixed together in an IV solution.
3. Use freshly prepared solutions for compounding.
4. Always verify correct diluent, IV fluid, drug, and final concentration before compounding.
5. Order of mixing additives affects the compatibility (e.g. add PO4 last to TPN)
6. Solutions should be administered promptly after mixing or within the stability window so that the occurrence of potential reactions can be minimized.
7. Always refer to compatibility references.
8. Visually inspect final product after compounding for integrity, leaks, solution cloudiness, particulates, color, and proper preparation.
9. Ensure proper labeling of final IV product with beyond use date and time.
Summary Main risk for incompatibility
Preparation of infusion admixtures
Simultaneous application of IV drugs
Addition of multiple electrolytes and drugs in same IV
Strategy to Prevent Incompatibility
Standardize IV drug therapy
Compatibility data from literature
Exercise professional judgment as to whether or not the reported data can be used in your situation