Dispensing II

PHA 6130 | BATCH 2022

FACULTY OF PHARMACY – UNIVERSITY OF SANTO TOMAS

LECTURERS: Ms. Marri Jmelou Roldan, RPh, MSc.

Ms. Michaella Odonio, RPh, MSc.
TRANSRIBED BY: Azores, 3FPH
Therapeutic Incompatibilities
REFERENCES: PPT, Lecture Video

THERAPEUTIC INCOMPATIBILITIES
• Includes drug interactions which occur at the site of
action
• Potentiation of therapeutic interactions between 2 or
more ingredients.
• Destruction of effectiveness of one or more
ingredients.
o Counteracts or cancels the effect of another
drug/ingredient
• Occurrence of toxic manifestations within the
patient. (worst condition, can lead to toxicity)
• •
IV DRUG COMPATIBILITY
• Physicochemical incompatibility (PCI) between drugs
infused together is frequent, but under-recognized.
• PCI can lead to
o drug inactivity (therapeutic failure)
o catheter occlusion
▪ usually occurs in the bloodstream due to
crystallization
o embolism due to crystallization and separation
o inflammatory reactions
o Tissue irritation due to pH change
o Damage from toxic products
o Death
▪ Some tend to neglect the possibility of
precipitation when preparing IV admixtures
and that can actually lead to embolism
which is fatal to the patient
• Tools proposed to reduce the frequency of PCI
include:
o compatibility cross-tables
o labeling of drugs with extreme pH
o optimized administration schedules.
▪ Excessive contact time with the drug (e.g.,
Large volume parenterals [LVP]) can lead to
incompatibility
Degree of dilution i
• generally, the more diluted the drugs are in a
solution, the less chance there is for an ion
interaction leading to incompatibility.
• In administering LVPs, hindi pa dapat siya puno. You
have to observe if the drug is somehow consumed
already, before refilling it to prevent over dilution.
Length of time in solution i
incompatibility increases with the length of time that
drugs are in contact with each other.
Order of mixing i
• Ex.: Calcium phosphate, should not be added
consecutively when an IV admixture is being
prepared.
• This keeps these substances from pooling or forming
a layer on top of the IV fluid, decreasing the chance
of incomp.
• Thorough mixing after each addition is essential
Other Examples i
1. Amphotericin B, cisplatin and metronidazole must be
protected from light.
o Dextrose bottles are not light resistant. In some
patients receiving LVP, it is wrapped in
aluminum foil.
2. Cefazolin is stable at room temperature for 24 hours
and 14 days if refrigerated.
3. Up to 10 mEq of Calcium can be added to each lite of
TPN containing 20 mEq of PO4
4. Bactrim 5mL/75mL D5W stable for 2 hours, whereas
5mL/125mL D5W is stable for 6 hours.
5. Amino acid composition and concentration in TPN
EXAMPLE OF A COMPATIBILITY TABLE

FACTORS AFFECTING IV COMPATIBILITY

pH i
• incompatibility is more likely to occur when the
components of an IV solution differ significantly in pH.
Explained by chemical reaction between an acid and
a base, which yields a salt and water; the salt may
form an insoluble ppt.
• can also indicate stability of drug
• most drugs are only stable at a certain pH, once there
is a change in pH problems may occur (e.g.,
insolubility and instability)

Temperature i
• increased storage temperature speeds up drug
degradation. To preserve drug stability, drugs should
be stored in a refrigerator or freezer as appropriate.

DISPENSING2 LAB| THERAPEUTIC INCOMPATIBILITIES 1|AZORES

 WAYS TO MINIMIZE OR PREVENT IV INCOMPATIBILITIES
1. Mix thoroughly when a drug is added to the
preparation.
o Ex. Dissolve in the solution completely
2. Minimize the number of drugs mixed together in an IV
solution.
o The lesser the number of drugs mixed in IV fluid,
the lesser the chance of having an
incompatibility
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 reaction can be minimized.
7. Always refer to compatibility references.
8. Always visually inspect final product after
compounding for integrity, leaks, solution,
cloudiness, particulates, color, and proper
preparation.
o Check for clarity
9. Ensure proper labeling of final IV product with beyond
use date and time.
PARENTERAL NUTRITION (PN)
FACTORS FOR INCOMPATIBILITIES WITH PARENTERAL
NUTRITION
1. Precipitation of Calcium and Phosphate
2. Creaming/ cracking of the liquid emulsion
3. Addition/ simultaneous application of drugs to/ with
PN.
PREVENTING OR MINIMIZING INCOMPATIBILITIES
CRITERIA FOR DRUG COMMONLY ADDED TO PN
ADMIXTURES (e.g., INSULIN, HEPARIN, AND FAMOTIDINE)
1. Stable dosage regimen over 24 hours
o PN & IVF are usually given for 24 hours
2. Pharmacokinetic profile supporting 24-hour infusion
3. Stable PN solution infusion rate
4. Documented chemical and physical stability over 24
hours
HOW TO AVOID INCOMPATIBILITIES WITH PN?
1. Never use PN for electrolyte therapy
o Remember that PN is different from IVF
2. Be familiar with manufacturer’s recommendation
o Read manual / insert
3. Add divalent cations (calcium and magnesium) and
phosphate as organic bound salts (e.g. gluconate)
4. Do not add drugs or Iron to PN
5. May piggy back lipids separately
o In administering lipids, use piggy back
6. Avoid Y-site administration of drugs with PN
DISPENSING2 LAB | THERAPEUTIC INCOMPATIBILITIES
CORRECTION OF INCOMPATIBILITIES
• consult the physician
o Regarding modification / alteration of the
prescription
o Whenever you call the attention of the doctor,
you should also have an evidence about the
problems in the prescription and a
recommendation which is evidence-based as
well.
• use pharmaceutical knowledge
• add an ingredient
o e.g., using superimposition, +inert ingredient to
absorb the water
• remove an ingredient
o Act of omission; If the ingredient does not have
any or has less therapeutic value in the
prescription
• change the vehicle
o If you notice that the active ingredient is organic
and the vehicle is inorganic/aqueous in nature
then we can change the vehicle or do post-
solvency system
• change an ingredient
o Ex. If your vehicle is water and you are using an
alkaloid, you can change the free form of the
alkaloid to its salt form to increase its solubility.
• change the dosage form
o We usually change the solution into a suspension,
because solutions tend to precipitate unlike
suspensions
• read the literature
• Each drug should be mixed thoroughly after it is added
to the preparation
• Solutions should be administered promptly after they
are mixed to minimize the time available for a
potential reaction to occur
o Especially if the product has a delayed
incompatibility
• The number of drugs mixed together in an IV solution
should be kept to a minimum
• If a Rx calls for unfamiliar drugs or IV fluids,
compatibility references should be consulted
o Drugs.com - to check for drug incompatibilities
2|AZORES